Keywords fetal brain - first trimester screening - holoprosencephaly - migrational disorders - ganglionic eminence
Introduction
Since the introduction of first-trimester screening, increasing attention has been
paid to early diagnosis of fetal structural abnormalities at weeks 12–14, in
particular the fetal brain has received much attention in recent years.
Complementing our two publications showing the possibilities of detailed analysis of
supratentorial structures of the fetal brain – future cavum septi pellucidi (fcsp),
cavum veli interpositi (cvi), third ventricle (3rd v), ganglionic eminence
(GE) and thalamus/hypothalamus (Th/HyT) – in GW 12–14, this study presents the
expanded possibilities for the diagnosis of pathological changes.
Materials and Methods
This was a retrospective, cross-sectional observational study including examinations
between 2016 and 2023 presenting with various malformations on ultrasound and/or
pathologic genetic analysis during first-trimester screening. Local ethics committee
approval was obtained. Transvaginally acquired 3D volume blocks of the fetal brain
of the selected fetuses were shown in excellent quality. GE ultrasound machines
(E10), equipped with a transvaginal 3D probe 6–12 MHz, were used for the acquisition
of the volume blocks and for the analysis of the structures. The imaging as well as
the analysis of the structures were performed according to the parameters published
in our previous studies on the structures of the supratentorial brain and CRL
(crown-rump-length) 45 to 84 mm [1 ]
[2 ]. The following were analyzed: f uture
C avum S epti P ellucidi a ntero-p osterior and
c ranioc audal (fCSP ap cc ), third ventricle
antero-posterior, craniocaudal and lat eral (3
rd
v
ap cc lat) , C avum V eli I nterpositi ap and cc (CVI ap
cc) , g anglionic e minence ap in an axial plane (GE ap –
axial), the distance g anglionic e minence/i nsula lateral
(GE/I lat) , g anglionic e minence/b asal g anglia
lateral (GE/BG lat) , g anglionic e minence/b asal
g anglia in a co ronal plane (GE/BG co ),
th alamus/hy pothalamus craniocaudal and lateral (Th/HyT cc
lat ). The above parameters were analyzed sonomorphologically and with regard
to the normal values of our previous studies [1 ]
[2 ]. For cvi lateral we used
Loureiro’s normal values published in 2012 [3 ].
The volume blocks stored during the initial examination were subjected to an initial
analysis immediately after completion of the examination, after the confirmation of
pathological brain changes a second analysis and correlation was done.
All pregnant women were offered genetic testing: fluorescence in situ hybridization
and karyotyping, followed by micro array and HPO (human phenotype ontology) term
based analysis if necessary. All pregnancies that were not terminated at the
parents’ request after abnormal genetic findings were further monitored by
ultrasound until the suspected changes could be clarified.
To improve interpretability, fetuses were divided into a group of classical numerical
chromosomal aberrations and a group of typical organic changes on ultrasound. The
subgroups and the overlap of both groups are shown in [Table 1 ]. The idea of the different groups was
to summarize all available cases differently to show how high the probability of
brain changes was in the respective groups. All other fetuses not assigned to any of
the above groups were combined in a group including various genetic and syndromic
disorders with no overlap with the above groups.
Table 1 Classification of numerical chromosomal aberrations
in contrast to organic changes with illustration of overlap to better
show correlation with supratentorial pathologies.
a) Numerical Chromosomal Aberrations
Tris 21
Tris 18
X0/XXX
Tris 13
Tripl
b) Organic Changes
HPE
EEC
MMC
Total number
9
13
9
5
4
Total number
8
3
4
Organic findings
HPE
2
1
Genetic findings
Tris 13
2
Cavitations
1
Tripl
1
GE,Th enlargement
4
Mutation CEP Gen
1
No additional findings
8
13
9
3
Meckel Gruber
1
Norm. genetics
5
1
4
Supratent. normal
8
13
9
3
0
Supratent. normal
0
0
0
Supratent. abnormal
1
0
0
2
4
Supratent. abnormal
8
3
4
Result
Group of Numerical Chromosome Aberrations
In 44 of the 64 analyzed fetuses genetic testing revealed abnormal genetic
findings: nine cases of trisomy 21 (Tris 21), thirteen cases of trisomy 18 (Tris
18), five cases of trisomy 13 (Tris 13), four cases of triploidy (Tripl), nine
cases of sex chromosomal aneuploidies (eight X0 and one XXX), and four fetuses
presenting with various genetic disorders.
We found no dilatation of the ventricles in fetuses with isolated trisomy 21,
trisomy 18, and sex chromosomal aneuploidies, supporting the observation of
Manegold-Brauer that shrinking of the choroid plexus rather than dilatation of
the ventricles is the relevant factor for an increased probability of trisomy
21/18/13 [4 ]
[5 ]. In the trisomy 21 group, one fetus (fetus a) showed cavitations
of the GE in the frontal horns. A subsequent HPO (human phenotype ontology)
term-based analysis revealed two alterations in the DYNC2H1 gene of unclear
clinical relevance “variants of unknown significance” (VUS) that might explain
the unexpected cavitations of the GE.
In our group of five trisomy 13 fetuses we found two holoprosencephalies,
described later, one fetus showed dysplasia of the fCSP and pathological
narrowing of the CVI, one fetus showed no change in brain structures, a
distribution consistent with the statistical probability for brain changes in
trisomy 13 in the current literature [6 ].
Only in the triploidy group did all four fetuses show analogous changes –
enlargement of the GE and Th/HyT as a uniform expression of the malformation of
cortical development, representing typical expression of abnormal cell
production or reduced apoptosis, consecutively accompanied by a reduction of the
width of cvi and 3rd v. One fetus showed an additional absent fCSP
[6 ].
In the heterogeneous group of diverse genetic alterations ([Table 2 ]) – Cenani Lenz Sy,
Microduplication 1q21, Noonan Syndrome, Gorlin Goltz Sy – only one fetus (fetus
b) showed brain alterations – dysplasia of the fcsp according to the described
morphological and metric criteria, detectable in this fetus already at weeks
12–14, was confirmed by MRI and is an occasional additional pathologic finding
in Gorlin Goltz Syndrome (ORPHA:377). The brain development of all 4 fetuses was
confirmed after birth.
Table 2 Various syndromic and genetic
disorders.
Genetic testing
Brain development
OS
Outcome
Disorder
Normal
Disorder
Normal
Cantrel Pentalogy
2
0
2
n
TOP
Ectopia cordis
1
0
1
n
TOP
Cenani Lenz Syndrome
1
0
1
j
TOP
Noonan Sy
1
0
1
j
TOP
Microd. 1q21
1
0
1
j
Birth
Complex Malformation Sy.
2
0
2
j
TOP
Gorlin Goltz-Sy
1
1
j
Birth
fetus b
Severe Microlissencephaly
1
1
n
TOP
fetus c
Interhemispheric Arachnoid Cyst
1
1
j
Birth
fetus d
Lissencephaly Type 2
1
1
j
TOP
fetus e
Severe Hydrops
1
1
j
TOP
fetus f
Group of Organic Changes
Group of Encephaloceles
All three described occipital encephaloceles (EEC) showed alteration or dysplasia
of the 3rd v and cvi. While one fetus (normal chromosomes) showed an
occipital meningoencephalocele with an elliptic penetrating planum of
14.4 x 8.8 mm, the second fetus with a penetrating planum of 11mm revealed
penetration of the meninges only (occipital meningocele). In addition, this
fetus showed a mutation in the CEP gene. Fetus three in this group showed the
most severe alteration with an elliptic large penetrating planum of 14 x 9 mm
and additional severe dysplasia of the cerebellum and mesencephalon, genetically
verified as Meckel-Gruber syndrome [7 ].
Group of Myelomeningoceles
All four fetuses with spina bifida (myelomeningocele - MMC) showed a reduced
lateral width of the third ventricle and cvi (roof of the third ventricle)
according to the study by Loureiro [3 ].
Holoprosencephaly Group
In the group of holoprosencephalies (HPE) we found two alobar holoprosencephalies
showing a typical monoventricle and one semilobar HPE presenting with the
typical fusion of the anterior horns and preserved separation of the posterior
horns [8 ]
[9 ].
Of particular scientific interest, however, is the diagnosis of the lesser
varieties of HPE, three MIH (middle interhemispheric variant) [10 ]
[11 ], and two lobar HPE in our collective where we were able to
demonstrate parenchymal bridge frontal, dorsal, and parietal, respectively, as a
common and typical main feature in analogy to later gestational weeks [12 ].
MIH variants typically present with a lack of separation of the parietal and
posterior frontal lobes, an expression of the isolated fusion of these regions,
while the regular separation of the polar portions of the brain is preserved. On
ultrasound, an arcuate gap is the typical sign in the sagittal plane beginning
anterior to the altered third ventricle, instead of the dorsal portion of the
frontal lobe expected in the area and the absent fcsp extending arcuate dorsally
over the thalamus above the dysplastic CVI ([Fig. 1 ]). Complementary to the typical image of the midsagittal
presentation, the axial image of the MIH variant can be used to establish the
tentative diagnosis, the exact differentiation of the fusion of the individual
lobes remaining reserved for the midline diagnosis.
Fig. 1 (HPE MIH variant): fetus 2, CRL 57 mm (a )
midsagittal plane (b ) axial plane (c ) coronal plane:
asterisk – typical figure showing MIH interventricular connection
(parietal and posterior frontal lobes fused); plus/conj 3.v – conjoined
third ventricle; (adjacent lateral walls of the 3rd v); arrowhead/dspl.
CVI – dysplastic cavum veli interpositi; interhem. fissure –
interhemispheric fissure; dyspl. GE – dysplastic ganglionic eminence
(reduced in size, clearly shown in [Fig.
1c ]); par. bridge – parenchymal bridge; ah – anterior horn; ph
– posterior horn; pit. gl – pituitary gland; DW - Dandy Walker
Malformation, ref. [Fig. 1c ] –
reference line showing the plane of [Fig. 1c ].
Most difficult to diagnose in early pregnancy is lobar HPE typically defined by
the absence or dysplasia of the fCSP and parenchymal bridge, the only feature
allowing the differentiation from the corpus callosum malformation group ([Fig. 2 ]).
Fig. 2 (lobar HPE): fetus 4, CRL 76.9 mm (a ) axial plane
(b ) midsagittal plane: par. bridge – parenchymal bridge;
interhem. fissure – interhemispheric fissure; asterisk – dyspl. choroid
plexus of the third ventricle, enlarged filling cavum veli
interposition; Fo. of Monroe – Foramen of Monroe; conj. 3.v – conjoined
third ventricle; Aq – aqueduct
The fluid gap of the 3rd ventricle is clearly narrowed or absent in
our collective except for in two cases. In one of the cases (fetus 7), the
3rd ventricle dilates together with the cvi into a dorsal cyst,
and in the second fetus the dilatation of the third ventricle is part of the
described typical MIH change, the fusion of the ventricles, extending into the
3rd ventricle (fetus 5). Consistently valid for all cases in our
collective is the absence of the fCSP. Imaging and measurements of the GE
revealed a wide variation of dysplasia (hyperplasia to hypoplasia to aplasia).
In contrast to the presentation of the GE, the thalamus also revealed a wide
range of dysplasia without showing a clearly discernible pattern. Consequently,
HPE in early pregnancy can be divided into its subgroups. Its expression as a
continuum with variations analogous to the changes in the later weeks of
gestation makes a clear classification difficult in some cases. Nevertheless,
the differentiated analysis of the changes to be expected allows an initial
clinical assessment. [Table 3 ] shows a
sonomorphological classification based on Hahn 2010 [13 ]. Pathological changes in the
measurements are listed in [Table 4 ]. In
some cases, with pronounced hypoplastic ganglion eminence, the measurements
resulted in 0 mm due to the fact that the defined measurement planes were
situated above the severely dysplastic structure of the GE.
Table 3 Neuroimaging features of various types of HPE in
early pregnancy.
Fetus 1
Fetus 2
Fetus 3
Fetus 4
Fetus 5
Fetus 6
Fetus 7
Fetus 8
Cortical hemisphere fusion
Frontal and parietal
Dorsal anterior/superior
Complete
Dorsal anterior
Dorsal anterior/super
Dorsal anterior/superior
Dorsal anterior
Holosphere
Interhemispheric fissure and falx cerebri
Only present in a posterior location
Present in the anterior and posterior poles
Absent
Hypoplastic anterior
Hypoplastic anteriorly
Hypoplastic anteriorly and superiorly
Hypoplastic anteriorly
Absent
fcsp
Absent
Absent
Absent
Absent
Absent
Absent
Absent
Absent
Lateral ventricles
Fusion of the anterior half
Fused at their middle portion (body)
Fused
Fused superior
Fused at their middle portion (body)
Fused at their middle portion (body)
Small fusion anterior
Monoventricle
3rd ventricle
Almost completely adh,
Almost completely adherent, dysplastic
Almost completely adherent, dysplastic
Almost completely adherent, dysplastic
Enlarged
Almost completely adherent, dysplastic
Caudal adherent, cranial opening into dorsal cyst
Almost completely adherent, dysplastic
cvi
Extremely small
Very small
Dysplastic
Dysplastic
Enlarged
Hypoplastic
Opens into the dorsal cyst
Fused, hypoplastic
Dorsal cyst
None
None
Present
None
None
None
Present
None
Ganglionic eminence
Asymmetric, dysplastic, very small
Hyperplastic
Hypoplastic, dysplastic
Hypoplastic
Hypoplastic dysplastic
Hyperplastic/dysplastic
Dysplastic/hypoplastic
Absent
Thalamus/hypothalamus
Normal size
Dysplastic
Normal
Normal
Separated, enlarged due to 3.v
Dysplastic
Partially fused
Fused, hypoplastic
Parenchymal bridge
Frontal
Superior
Anterior
Anterior
Anterior/superior
Anterior and superior
Anterior
Anterior
Fossa post
DW variant
DW
DW
DW
Aqueductal stenosis
Normal
Normal
Norm
HPE type
Semilobar
MIH
Alobar
Lobar
MIH
MIH
Lobar
Alobar
Face
Facial cleft
Retrogeny
Proboscis, hypotelorism
Bilat facial cleft
Bilat facial cleft
Normal
Bilat facial cleft
Proboscis, hypotelorism
Genetic
Normal
Triploidy
T13
T13
normal
Normal
Normal
Normal
Table 4 Presentation of values of
holoprosencephalies.
Cerebral plane
Sagittal fCSP
Sagittal 3v
Sagittal CVI
ax GE
co GE/BG
co Th/3v/VCIO
ID
CRL
fCSPap
fCSPcc
3v ap
3v cc
CVI ap
CVI cc
GE ap
GE/I
GE/BG lat
GE/BG cc
Th lat
Th cc
3.V lat
VCI lat
fet 1
56.6
0
0
5
7.6
0.04
0.05
0
0
0
0
7
6.1
0.06
0.03
fet 2
57.0
0
0
6.2
5.2
0.07
0.07
12.8
6.8
5.3
5.6
10.9
7.9
0.03
0.02
fet 3
61.3
0
0
5.4
9.9
2.6
1.2
0
0
0
0
7.6
6.7
0.05
0.07
fet 4
76.9
0
0
6.5
6.7
2.7
2.2
5.5
3.3
2.1
2
10.5
7.6
0.7
0.8
fet 5
79.5
0
0
10.8
10.5
7.5
3.7
5
3.3
2.2
2.8
12.2
5.7
1.9
1.7
fet 6
80.4
0
0
5.9
9.7
0.2
0.1
7.7
7.9
6.5
6.2
12.2
8.7
0
0
fet 7
80.9
0
0
6.8
8.2
5.2
n. a.
0
0
0
0
9.9
6.5
1.9
6.1
fet 8
81.8
0
0
7.2
8.7
0
0
0
0
0
0
8.8
7.2
0
0
Measurements in correlation to the standard values taken in the published
standard planes – fCSP; 3.V; CVI ap.cc GE; Th (Altmann) – CVI lat (roof
of 3.V) Loureiro Measurements>97% bold. Measurements<3% light
italics.
Group of Cavitations
In our collective, two fetuses were found with bilateral cavitations in the
ganglionic eminence region. In fetus a the cavitations were attributed to a very
rare genetic alteration, diagnosed subsequently in the course of whole exome
sampling designated as VUS (see above) in addition to a free trisomy 21
previously diagnosed in the same fetus, whereas the very pronounced cavitations
in fetus c were part of a complex brain malformation, which we diagnosed as
microlissencephaly in perfect compliance with all changes in the description by
Prefumo [14 ].
Group of various syndromic and genetic disorders
In the group of fetuses with various syndromic and genetic disorders without
overlap to the groups presented above, Fetus a (CRL 54 mm) presents with
cavitations described earlier. Fetus b (CRL 60 and 83 mm) (
[Fig. 3 ]
) showed aplasia of the fCSP
at a CRL of 60 mm and hypoplasia of the fCSP at 83 mm. In week 26 a dysplastic
corpus callosum was confirmed by MRI. Genetic diagnosis of Gorlin Goltz Sy was
confirmed ([Fig. 3 ]). Fetus c (CRL 45.6
mm) (
[Fig. 4 ]
) showed huge
bilateral cavitations of the ganglionic eminence, an enlarged GE, an absent
fCSP, a hypoplastic thalamus, a hypoplastic 3rd v and CVI.
Infratentorial the vermis showed the typical shape of a DW malformation
(hypoplasia and uprotation of the vermis). Genetic testing revealed normal
chromosomes including WES. Follow-up was rejected by the mother. In summary, we
diagnosed microlissencephaly, also with regard to the extracranial changes in
the fetus ([Fig. 4 ]) [14 ]. Fetus d (CRL 66 mm und 73 mm)
showed an absent fCSP, reduced craniocaudal length of the 3rd v, an
absent CVI, a dysplastic GE, Th/HyT, and an interhemispheric arachnoid cyst. The
diagnosis was confirmed in GWs 15+6 and 19+6 (details and figures published in
2022) [1 ]. Fetus e (CRL 79mm) showed
hypoplasia/dysplasia of the GE and Th/HyT. The fCSP was hypoplastic, the CVI was
elongated, and the cerebellar vermis and transcerebellar diameter were reduced.
At GW 16+3, the cerebral malformations were confirmed, leading to the diagnosis
of cobblestone malformation (details and figures published in 2023) [2 ]
[15 ].
Fetus f (CRL 60.1 and 83.4mm) presented with severe hydrops. Detailed
analysis of the fetal brain revealed serious enlargement of the 3rd v
and cvi. The ratio between the choroid plexus and lateral ventricle diameter,
between the choroid plexus and lateral ventricle length, and between the choroid
plexus and lateral ventricle area were normal. Infratentorial the vermis
presented hypoplastic and uprotated [16 ].
In contrast, the control at week 15+5, 16+6 showed normal supratentorial
structures including a normal cvi and 3rd v ([Fig. 5 ]).
Fig. 3 (absent/hypoplastic fcsp): fetus b, CRL 60.0 mm (a )
midsagittal plane (b ) axial plane; CRL 83.8 mm (a )
midsagittal plane (b ) axial plane: abs. fcsp – absent future
cavum septi pellucidi; fcsp small – future cavum septi pellucidi<3.
percentile; Ch.p.3.v – choroid plexus of the third ventricle; pit. gland
– pituitary gland; Aq – aqueduct; Ve – vermis cerebelli; distance GE/I –
normal distance ganglionic eminence to insula; 3.v – third ventricle; ah
– anterior horn.
Fig. 4 (microlissencephaly): fetus c, CRL 45.6 mm (a ) axial
plane (b ) coronal plane: GE Cavitations – cavitations of
ganglionic eminence on both sides to varying degrees; asterisk/dyspl. Th
– dysplastic thalamus.
Fig. 5 (enlarged 3rd v/CVI): fetus f, CRL 60.1 mm. (a )
midsagittal plane (b ) axial plane; CRL 83.4 mm (c )
midsagittal plane; GW 15+5 (d) axial plane: distance CVI ap – enlarged
distance of cavum veli interpositi anteroposterior; distance 3.v lat –
distance third ventricle lateral (enlarged in b, normal in d); arrowhead
fcsp – future cavum septi pellucidi; arrowhead corpus callosum – corpus
callosum; Ch.p.3.v – choroid plexus of the third ventricle; comm. plate
– commissural plate; opt. chiasm – optic chiasm; pit. gland – pituitary
gland; DW – Dandy Walker Malformation; asterisk – severe hydrops
fetalis.
All measurements of the presented fetuses are shown in [Table 5 ].
Table 5 Presentation of values of syndromes and genetic
disorders.
fet a
54.0
1.3
1.3
5.9
9.1
3.2
1.5
5.2
2.3
1.4
1.3
7.0
6.2
1.1
1.1
fet b
60.0
0
0
6.5
9.6
4.5
1
6
3.3
2.7
3
8.3
7.8
0.9
0.9
83.8
0.9
2.1
7.6
12.1
4.2
1.5
10.4
5
3.7
3.7
11.5
8.3
1.8
0.8
fet c
45.6
0
0
4.3
5.9
2
1
7.3
7.7
7.2
6.5
4.3
4
2
0.7
fet d
66.2
0
0
8.7
9
0
0
6
6
4.5
3.1
10
8.5
0.7
0
73.0
0
0
9.3
11.4
0
0
7.2
6.6
4.6
3.2
12.6
7.8
1.7
0
fet e
78.9
0.9
1.2
7
11.2
6.6
2.2
0
0
0
0
11.8
6.7
2.9
1.3
fet f
60.1
1.2
1.2
6.5
10.6
6.6
2
6.4
3.8
3.0
2.8
8.2
7
2.1
1.7
83.4
1.7
1.9
8
10.6
8
3
9.2
5.5
4.0
3.9
11
9.3
1.7
1.5
Measurements in correlation to the standard values taken in the published
standard planes – fCSP; 3.V; CVI ap.cc GE; Th (Altmann) – CVI lat (roof
of 3.V) Loureiro Measurements>97% bold. Measurements<3% light
italics.
The average BMI of the women was 23.01. The average length of the fetuses was
65.93 mm crown rump length.
Discussion
Ganglionic Eminence
The classification of malformation of cortical development (mcd) as enlarged
(excessive proliferation or reduced apoptosis), reduced (reduced proliferation
or increased apoptosis), and cavitations used by Contro 2023 [17 ] for pathological changes of the GE in
weeks 19 to 22 is analogously applicable to our earlier collective.
Cavitation of the GE was first described by Righini in 2013 [18 ] on MRI. Prefumo described it on
ultrasound in 2019 [14 ], while Brusilov
described choroid plexus cysts in week 15 [19 ]. The two cases we found in our collective, one being part of a
severe malformation of the brain ([Fig.
4 ]), in complete analogy to Prefumo’s case, was diagnosed as
microlissencephaly, while the second, smaller cavitation was interpreted as a
product of trisomy 21 and two alterations in the DYNC2H1 gene of unclear
clinical relevance “variants of unknown significance” (VUS).
According to this classification, the enlarged MCD group included all four
triploidies and one HPE, and the group of reduced MCD included eight out of nine
cases of HPE. Lissencephalies, due to their very heterogeneous causality, were
distributed over all 3 groups of MCD. In addition to the cases found in our
collective of GE changes representing pathological cell proliferation,
migration, and apoptosis, ischemic, destructive, or infectious processes must
also be considered for differential diagnosis, even in early pregnancy.
fCSP
The use of fCSP imaging for the diagnosis of pathologies of the corpus callosum
is novel as a method and is described in this study. The absence of the fCSP in
all holoprosencephalies is congruent with the described changes in the later
weeks of pregnancy. The absence of the fCSP in triploidy is congruent with the
described literature. Unfortunately, direct evidence is missing because all
pregnancies were terminated after early pregnancy.
However, three of the described isolated fCSP pathologies could be proven by
investigations in the later weeks of pregnancy (fetuses b, d, and e). As a
special detail, we note that the fCSP was not able to be represented at a CRL of
60 mm in one of the fetuses, whereas the fCSP showed a dysplastic reduction at a
CRL of 83 mm, reflecting corpus callosum dysplasia later verified by MRI (fetus
b, [Fig. 3 ]).
HPE
In our study we were able to show that with detailed knowledge of the anatomical
structures and using transvaginal 3D examinations it is possible to diagnose
lesser varieties of HPE under good examination conditions, thereby extending the
most recent study by Montaguti 2022 [12 ] to
include the possibilities of early diagnosis in weeks 12–14. For a better
representation of the changes, we adapted the table prepared by Hahn 2010 [13 ] to point out the typical changes of the
early weeks of gestation ([Table 3 ]).
Special reference should be made to the MIH variant (fusion of the dorsal parts
of the frontal and parietal lobes) and its diagnostic possibilities ([Fig. 1 ]). The differentiation of the
isolated absence of the fCSP as an expression of agenesis of the corpus callosum
in the later weeks of gestation from lobar HPE, which only differs from the
former with respect to the parenchymal bridge, remains to be classified as
particularly difficult ([Fig. 2 ]). The
different degree of adhesion of the thalami resulting from a fusion of the
medial margins of the two thalami separated in early pregnancy [20 ] being formed in our study period was not
helpful for the differential diagnosis of the HPE variants. While alobar,
semilobar holoprosencephaly and the MIH variant [21 ], which are already well defined in GW 12–14, are only given
additional criteria by our analysis, the ultrasound images of lobar
holoprosencephaly in GW 12–14, clearly following the criteria applicable in
later weeks of gestation, define new diagnostic criteria where no follow-up or
histological workup is available in our collective.
CVI/3rd V
The changes of the 3rd ventricle in our collective were mainly attributable to
general dysplastic changes such as HPE or triploidy. Isolated changes, as
described for MMC by Loureiro [3 ], could be
reproduced, both the lateral measurements of the roof of the 3rd ventricle (now
CVI) and the values of the 3rd ventricle, measured below the attachment site of
the choroid plexus of the 3rd ventricle.
Furthermore, it was our intention to find out the extent to which changes in
early aqueductal stenosis could influence the width of the 3rd v
[22 ]. Analogously, we also sought to
answer the question of whether an enlargement of the suprapineal recess
(measurement parameter CVI ap) could be diagnostic for early aqueductal stenosis
[23 ]
[24 ]. Both hypotheses had to be rejected as inapplicable. Aqueductal
stenosis does not dilate the 3rd ventricle nor enlarge the suprapineal recess.
In contrast, we found marked enlargement of the 3rd V and CVI in one
fetus, which disappeared later in pregnancy. An explanation for this finding is
lacking ([Fig. 5 ]).
Limitations: Despite all the detailed analyses described in our study, it must be
emphasized that for the time being all the pathologies require further
scientific analysis. Above all, however, scientific knowledge has shown in
recent years that the development of brain structures can be subject to
significant individual fluctuations. As a result, a clear warning should be
issued against deriving decisions based on a single ultrasound diagnosis in GW
12–14. The performance of further 3D ultrasound or MRI examinations to confirm
diagnoses of the developing brain should be state of the art.
Summary
Our study demonstrates that pathologic changes of the brain in weeks 12–14 (CRL
45–84 mm) can be diagnosed with precise knowledge of the anatomical conditions and
with the use of appropriate high-resolution ultrasound equipment. For this reason,
we recommend the presentation of suspected brain anomalies in weeks 12–14 at
specialized centers.
Bibliographical Record
