Introduction

Neural tube defects (NTDs) are caused by a failure of closure of the neural tube before the end of the sixth week of gestation at the two most vulnerable locations (i.e., the rostral and caudal neuropores). Dorsal induction failures are divided into open and closed defects and classified according to the level of the lesion.

Failure of the rostral and caudal neuropores to close during the primary neurulation results, respectively, in cranial and spinal open NTD. Failure of the canalisation during the secondary neurulation results in closed NTD. Causes of NTD are multifactorial, involving genetic and mainly epigenetic risk factors along with complex mechanisms.

At the spinal (caudal) level, an NTD is called spinal dysraphism or SB.

When a spinal column defect remains covered (closed SB) rather than open (open SB), fetuses do not develop the same severe sequelae. In its open form, SB presents as a progressive disease explained by the two-hit pathogenesis. First, there is the failed closure of the neural tube by the sixth week of gestation. Second, from 16 weeks onwards, there is secondary damage to the exposed spinal cord and nerves caused by direct trauma and neurotoxic agents in the amniotic fluid, as well as to the brain. The latter is evidenced by the development of VM and Chiari II malformation (CM) caused by CSF leakage at the level of the defect, leading to a ‘suction gradient’. A similar two-hit pathogenesis could explain the other types of NTD. For anencephaly, animal studies and case reports have shown that there is progression from acrania to exencephaly and finally anencephaly caused by secondary degeneration of the brain.

A study of long-term trends in prevalence of NTDs in Europe from 1991 to 2011 found that total prevalence fluctuates slightly but without an obvious downward trend. SB is the most frequent NTD with a total prevalence of 4.9 in 10,000 in Europe from 2008 to 2012 according to the European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registry, 3.17 in 10,000 in the United States, 1.4 in 10,000 in Brazil, and 15.0 in 10,000 in Northern China. Anencephaly and encephalocele have, respectively, a total prevalence of 5.40 and 1.06 per 10,000 births in Europe. Thanks to primary prevention in North America using folic acid food fortification, the total prevalence rate of SB in the United States declined by 31% from the pre- (1995–1996; 5.04 in 10,000) to the postfortification period (1998–2006; 3.49 in 10,000). In addition, preconception folic acid supplementation might also reduce the severity of NTD.

Prenatal screening for NTD by ultrasound in Europe showed detection rates ranging from 25% to 94%, with an overall detection rate of 84%. Detection rates depend on the presence of standardised screening programs, the gestational age at which screening is performed and the type of lesion.

Cranial Neural Tube Defects

Anencephaly and Exencephaly

The three phases in the development of anencephaly are (i) a defective development of the cranial vault resulting from a failed closure of the rostral part of the neural groove, (ii) exposure to the amniotic fluid and involuntary fetal movements changing the developing brain to amorphous neurovascular tissue (exencephaly) and (iii) a disintegration of the brain tissue resulting in anencephaly.

Sonographically, exencephaly is recognised by the bulging brain above the orbits (the Mickey Mouse Face or the French bonnet sign). Early in gestation, therefore, the diagnosis may be missed because the crown–rump length (CRL) may be normal. Complete disintegration of the brain subsequently results in a short CRL for gestational age and the typical frog-like appearance of the fetal face caused by the absence of any structure above the orbits ( Figs. 28.11 and 28.12 ). Differential diagnoses are large encephalocele and amniotic band syndrome ( Fig. 28.13 ). Sonographic detection of anencephaly reaches 100%, most of which occurs now in the first trimester. Associated anomalies are present in 25% to 50% of the cases. In isolated cases, the risk for chromosomal defects is low.

In exencephaly, the fetal brain tissue (arrowheads) bulges out of the skull as an irregularly shaped structure. The absence of the cranium is evident in this 12-week fetus.

Three-dimensional image of a fetus with anencephaly.

Large encephalocele (arrows) containing the midbrain ( ° ) and the occipital lobes (asterisk) on the axial plane.

Anencephaly is fatal prenatally, intrapartum or within 48 hours of birth.

Cephaloceles result from a defect in the skull and dura mater with protrusion of meninges (cranial meningocele) or herniation of brain tissue covered by meninges (encephalocele). Their pathogenesis resulting directly from failure of neural tube formation has been contested. However, at present, these lesions are still considered postneurulation disorders. Cephaloceles are usually covered by skin or a thin epithelium layer, occur most frequently at the midline and may involve the occipital (75%–85%), frontal (12%), eccentric parietal (13%–15%) and interparietal regions. The size of the lesion may vary considerably; occasionally, the size of the encephalocele is larger than the fetal head, which, because of the herniation, becomes microcephalic.

Infants with encephaloceles, especially giant encephaloceles, present with additional cerebral and extracerebral malformations in 20% to 36.8% of the cases ( Table 28.3 ). Syndromic forms such as Merkel-Gruber syndrome and Walker-Warburg syndrome carry an increased recurrence risk. Chromosomal abnormalities are rare. Prenatal ultrasound has great potential in the early detection of encephaloceles, even in the first trimester. Efforts should be taken to highlight the associated malformations and offer invasive prenatal testing, particularly in nonisolated cases. Differential diagnosis includes amniotic band syndrome, iniencephaly, cystic hygroma and scalp cysts ( Fig. 28.14 ).

TABLE 28.3

Encephalocoele: Associated Malformations

Group	Anomalies
Central nervous system	Corpus callous agenesis, intracranial cysts, tectorial malformations, Dandy-Walker, cerebellar vermis agenesis, ventriculomegaly, hydrocephaly, grey matter heterotopia
Nonsyndromic	Ventricular septal defect, aortic coarctation
	Cleft palate
	Tracheoesophageal fistula, gastroschisis, diaphragmatic hernia
	Costal malformations, talipes
	Pyelectasis, ureteral agenesis
Chromosomal abnormality	Trisomy 13, trisomy 18, mosaic trisomy 20, 13q-, monosomy X
Syndromic forms	Meckel-Gruber syndrome
	Walker-Warburg syndrome
	Knobloch syndrome
	Apert syndrome
	Fronto-facio-nasal dysplasia
	Oculo-encephalo-hepato-renal syndrome
Vascular	Vertical positioned straight sinus, elongation of the vein of Galen, fenestration of the superior sagittal sinus

 

Axial T2 half-Fourier acquisition single-shot turbo spin-echo (HASTE) image of the brain at 27 weeks and 4 days’ gestation. The small cystic structure in the left parietal area with tapering towards the bone (arrow) suggests a connection with the subarachnoid space: a small encephalocele.

In isolated encephaloceles (73%–80%), the prognosis depends on the site, the size and the content of the lesion. In nonisolated cases, the mortality rate is as high as 79%. Surviving neonates present with neurologic impairment in 75% to 80% of the cases, including seizures and significant developmental delays. In giant encephaloceles, TOP may be offered. Microcephaly and hydrocephaly are good indicators of an impaired outcome.

Small lesions without brain tissue may have surgical correction with good outcome. Caesarean section is performed for the larger lesions containing brain tissue to prevent trauma.

Craniospinal Defects

Craniorachischisis

Only 3% of NTDs display the most extreme form of primary neurulation failure: absent development of the cranial vault and defective closure of the vertebrae and skin. Sonographically, this lethal condition translates into an anencephaly with prolongation into a myeloschisis. Most cases end in early fetal loss ( Fig. 28.15 ).

Cervical rachischisis with hyperextension of the fetal head as seen in iniencephaly. However, iniencephaly is a closed spina lesion.

Open Spinal Dysraphism

The classification of spinal dysraphism has been revised recently as shown in Fig. 28.16 .

Classification of spinal dysraphism.

Meningomyelocele

Open spinal dysraphism (OSD) consists of vertebral defects without skin coverage, exposing the neural tissue either directly to the amniotic fluid (myelocele or myeloschisis) or with coverage by a meningeal membrane (meningomyelocele).

Cerebrospinal fluid leaks into the amniotic cavity and may be responsible for the scalloping of the frontal bones (lemon sign on ultrasound). In addition, the cerebellum often herniates through the foramen magnum (Arnold-Chiari malformation type 2); obstructs the circulation of CSF, which may result in VM; and leads to reversal of the lemon sign after 24 weeks’ gestation ( Fig. 28.17 ). Reduced head circumference (HC) on ultrasonography is frequently part of the clinical spectrum of open NTD with 53% and 74% of the fetuses presenting with an HC below the 3rd and 10th centiles, respectively.

A–D, Characteristics of myelomeningocele (MMC): lemon sign ( A ), banana sign ( B ), transverse section of the spine with MMC ( C ) and sagittal section ( D ) showing angulation of the spine and MMC.

Screening for open NTDs by ultrasound relies on these cranial markers rather than on the direct features of the spinal lesion. In 99% of cases, at least one cranial marker is present before 24 weeks’ gestation ( Table 28.4 ). Other cerebral signs in the second trimester include the pointed deformity of the posterior horn, tectal beaking or elongation of the tectum or the presence of an interhemispheric cyst.

TABLE 28.4

Frequency of Cranial Markers in Open Neural Tube Defects

	<24 wk (%)	>24wk (%)	Overall (%)
Lemon sign	97–98	13	53
Banana sign (small cerebellum)	96–97	96	96
Effaced cisterna magna	93		93
Ventriculomegaly	75		75–81
Small biparietal diameter			61–74
Ventricular point	>75

 

The identification and evaluation of the extent of the lesion demand sonographic exploration of the spine in all three planes (see Fig. 28.17 ). The 12th rib may serve as reference point to describe the level, although about 6% of fetuses display an abnormal number of ribs. Multiplanar 3D exploration of the spine and thoracic cage offers a standardised method of exploring and defining each vertebral level ( Fig. 28.18 ). Moving in the sagittal A plane, the B plane shows the axial view of the vertebral bodies and the overlying skin, which is the optimal view to identify the spinal defect. However, the bony defect does not always correlate with the functional level, prenatal prediction of the neurologic disability and functionality may be inaccurate.

Three-dimensional multiplayer examination of the spine allows for accurate identification of the level of the spinal defect.

Recently, detection of open SB at the 11- to 13-week scan by visualisation of the intracranial translucency (IT) and posterior brain in the midsagittal plane gained increased interest. However, the sensitivity of these markers is low. In the hands of experts, the sensitivities of an absent IT and cisterna magna were 18% and 64%, respectively but increased significantly with the use of specific cutoff values to 45% and 73%, respectively. Other ultrasound features may enable a shift to first trimester diagnosis such as the reduction in the amount of intracranial CSF.

Fetal MRI has little additional value in the determining the level of the spinal defect, evaluation of the neural placode or detection of CM compared with experienced neurosonogram with high-resolution probes. This is due to the low spatial resolution of MRI compared with ultrasound, although this can be compensated with the high-contrast resolution. However, MRI is of value in the preoperative setting because of the essential anatomical information for the neurosurgeon before surgical planning. More subtle abnormalities such as callosal dysgenesis, periventricular nodular heterotopia, cerebellar dysplasia, syringohydromyelia, diastematomyelia and destructive lesions are more easily identified on prenatal MRI. The neurologic impairments associated with open NTDs are shown in Table 28.5 .

TABLE 28.5

Neurologic Impairment Associated With Open Neural Tube Defect

Open NTD	Lethal	Neurologic Impairment at Cranial Level	Neurologic Impairment at Spinal Level
Anencephaly	Yes a	Absence of cerebral hemispheres function	Absence of spinal cord function
Encephalocele	No	Mild (anterior EC) to severe (posterior EC) cerebral dysfunction: • Developmental delay • Cognitive dysfunction • Seizures • Hydrocephalus sometimes Requiring CSF shunting • Ataxia • Vision impairments • Rarely, Chiari 2 malformation, and Dandy-Walker malformation	Absent or mild (anterior EC) to severe (posterior EC) spinal cord dysfunction: • Spastic quadriparesis (sensory-motor limb deficits) • Bladder, bowel and sexual dysfunction • Orthopaedic disabilities
Open SB (MMC and myeloschisis)	No	Absent to moderate cerebral dysfunction: • Hydrocephalus sometimes requiring CSF shunting • Chiari 2 malformation leading to hindbrain dysfunction • Rarely, cognitive dysfunction, seizures, ataxia, vision impairments	Mild to severe spinal cord dysfunction: • Spastic paraplegia (sensory-motor lower limb deficits) • Bladder (continence), bowel (continence) and sexual (erectile) dysfunction • Tethered cord syndrome • Orthopaedic disabilities (clubfoot, scoliosis)

 

CSF, Cerebrospinal fluid; EC, encephalocele; MMC, myelomeningocele; NTD, neural tube defect; SB, spina bifida.

a Lethal prenatally, intrapartum or ≤48 hours of birth.

Closed Spinal Dysraphism

Closed NTD are characterised by vertebral defects covered by skin. In the classification proposed by Tortori-Donati lesions are subcategorised into defects with a subcutaneous mass and lesions without a subcutaneous mass. In the absence of a subcutaneous mass, lesions are often missed prenatally.

Tethered Cord Syndrome

The spinal cord is fixed in the vertebral canal because of adhesions, resulting in a limited or absent ascent of the tip of the medullar cone. During fetal development, the vertebral spine grows faster than the spinal cord, so that the medullar cone ascends from L3 and L4 at weeks 13 to 18, to L2 between 20 and 24 weeks.

Tethered cord syndrome can be congenital or acquired due to a complication of spinal injury or in relation to an NTD.

The conus medullaris presents on ultrasound as a needle-shaped triangular hypoechogenic structure between two echogenic lines at the caudal end of the spine. Some anatomical landmarks can be reference points to determine the level of the medullar cone such as the upper pole of the kidney (T11) and the most inferior rib (T12). In tethered cord, the medullar cone is positioned below L2 ( Fig. 28.19 ).

Occult spina bifida with myelolipoma (asterisk) and tethering of the spinal cord (arrowheads). Notice the small skin appendage (°) .

Split Cord Malformations

Diastematomyelia or split cord malformation describes the splitting of the lower thoracic or upper lumbar spinal cord into two hemicords by a bony or cartilaginous spur. The diagnosis is suggested by widening of the spinal canal in the coronal plane and an echogenic bony fragment underlying the intact skin ( Fig. 28.20 ). Other spinal malformations are often associated with this condition. The prognosis seems favourable in isolated cases.

Diastematomyelia is a closed spinal defect characterised by diplomyelia and a bony spur (arrowhead) .

Introduction

The development of the prosencephalon or forebrain into the telencephalic vesicles and the diencephalon results from a series of inductive processes starting at the fifth postovulatory week. The process of ventral induction responsible for the formation, cleavage and midline development of the prosencephalon also takes part in the formation of the midface. Defective development results in a variety of malformations often associated with facial involvement ( Table 28.6 ).

Holoprosencephaly

Holoprosencephaly (HPE) is a complex and heterogeneous forebrain malformation. As a result of a ventral induction failure, the prosencephalic vesicle fails to divide into the telencephalic and diencephalic vesicles. In addition, the failed outgrowth of the frontonasal process is responsible for a variable degree of midfacial maldevelopment.

The incidence of holoprosencephaly is estimated at 1 in 6000 to 1 in 16,000 live births and at 1 in 250 in early conceptions. There is no male-to-female preponderance, nor a higher prevalence related to ethnicity. Table 28.7 lists the potential aetiologies.

According to the degree of forebrain separation, four different types can be distinguished: alobar, semilobar, lobar and interhemispheric variant ( Table 28.8 ).

Holoprosencephaly often presents with a variable degree of midfacial maldevelopment, ranging from cyclopia and proboscis, severe hypotelorism and ethmocephaly, to arhinencephaly and a normal-appearing face. Occasionally, the sole indicator might be a single incisor.

The diagnosis of semilobar and alobar HPE is feasible from the first trimester of pregnancy by either transabdominal or transvaginal ultrasound ( Figs. 28.21 and 28.22 ).

In alobar holoprosencephaly, the prosencephalic vesicle persists as a large single brain vesicle, overlying the fused thalami.

Interhemispheric holoprosencephaly.

Three-dimensional ultrasound, inversion mode rendering or 3D sono-automated volume count (AVC) of the ventricular system and sonographic tomographic imaging may be helpful in defining the severity of the malformation and characterising facial malformations. MRI is of great additional value in depicting the features that differentiate abnormal brain formation and aids in the diagnosis and counselling of these cleavage disorders, which have a different prognosis depending on the severity of failure of ventral induction.

Because of its frequent association with chromosomal malformations, fetal karyotyping or comparative genomic hybridisation (CGH) should be offered routinely. The most frequently encountered chromosomal malformations are trisomy 13, del (13q), del (18p), trisomy 18, triploidy, dup (3p) and del (7) (pter+q32).) The high risk for syndromic HPE demands a search for additional structural anomalies; therefore a pathological investigation is recommended.

The empiric recurrence risk for HPE is 5% to 6%. If HPE occurs in the context of a chromosomal anomaly; the recurrence risk is usually less than 1%. In syndromic forms, the recurrence rates may increase up to 25% to 50%. Dominant inheritance with reduced penetrance explains the inheritance pattern of familial HPE.

The outcome of the different types of HPE has been summarised in Table 28.9 . TOP is usually offered for alobar, semilobar and interhemispheric forms of HPE.

Corpus Callosum Dysgenesis

The CC is the major commissure between the two cerebral hemispheres and plays an important role in the integration of information between the hemispheres. At about 12 weeks’ gestational age, the CC starts to develop from the lamina terminalis as a bundle of fibres that connects the two hemispheres. The development of the CC is closely related to the normal appearance of the septa pellucida. Anterior to the foramina of Monroe, the space between the septa is called the cavum cave septi pellucidi (CSP); posterior to this structure, it is referred to as the cavum vergae (CV) The CC, which is composed of four segments, starts developing from the 11th week of gestation with the genu, and subsequently the body, isthmus and splenium form. The rostrum, the most anterior part, develops later. Completion of the CC is achieved by 18 to 20 weeks of gestation. At the median surface of the cerebrum, the gyrus cinguli creates a partial girdle around the CC and follows the callosal curve.

Normal sonographic development of the anterior and posterior complex in the axial plane indicate adequate midline development; however, morphologic abnormality in both complexes is a strong indicator for midline abnormalities and cortical malformations. The midsagittal and the coronal views are the best planes to directly visualise the CC. In a midsagittal two-dimensional view, the CC appears as a thin anechoic space, delineated superiorly and inferiorly by two smooth echogenic lines. The complete visualisation and measurement of the CC is feasible from 18 weeks’ gestation onwards. Normative charts can be used to evaluate the length and thickness of the CC. Transvaginal ultrasound, multiplanar 3D and three-dimensional volume contrast imaging in the C-plane (VCI-C) imaging facilitate the proper identification. The midsagittal plane reveals the CC with all its neighbouring structures; the CSP, the CV, the cavum veli interpositi and the cingulate gyrus. Using colour-flow Doppler, the anterior cerebral and pericallosal arteries with their branches and the vein of Galen are easily displayed in the early second trimester.

The terminology to describe CC dysgenesis includes complete and partial agenesis, hypoplasia (thinning of the CC), hyperplasia (thickening of the CC) and morphologically oddly shaped CC. A prevalence of 1.4 and 0.4 per 10,000 live births for ACC and hypoplasia of the CC has been suggested, respectively. These figures may be an underestimate as a proportion of asymptomatic ACC patients escape detection.

Absence of the Corpus Callosum

Complete absence of the CC (ACC) results in an abnormal induction of medial cerebral convolutions determining a radiate arrangement of the cerebral sulci around the roof of the third ventricle. With ACC, the semicircular loop of the pericallosal artery is lost, and branches of the anterior cerebral artery ascend linearly with a radial arrangement. ACC has been associated with other cranial anomalies, such as abnormalities of the posterior fossa and interhemispheric cyst and neuronal migration disorders. Because the development of the CC coincides with cortical development, lissencephaly, heterotopia, polymicrogyria (PMG) and schizencephaly are often present. The rate of chromosomal anomalies is estimated at about 17.8%, including microdeletions for which array comparative genomic hybridisation might be considered. In addition, ACC-linked syndromes show an autosomal dominant, recessive or X-linked mode of inheritance. An OMIM (Online Mendelian Inheritance in Man) search results in more than 200 entries, of which Aicardi and Andermann syndromes are the more common. Occasionally, a metabolic aetiology is found, such as hyperglycemia without ketose, a pyruvate dehydrogenase deficiency or phenylketonuria.

Indirect sonographic features are often helpful when screening for the absence of the CC. The absent CSP should raise suspicion, and dilation of the atria and occipital horns (colpocephaly) shaping the lateral ventricles like teardrops is very suggestive for CCA ( Fig. 28.23A ). There is, however, no progressive VM. On a coronal view, the lateral ventricles are displaced laterally because of the failure of the bundles of Probst to cross the midline, making the anterior parts of the lateral ventricles look like bull’s horns. Often the third ventricle is enlarged and extends posterior and cranially. Because of the lack of communicating fibres, there is an increased distance between both hemispheres ( Fig. 28.23B ), which shows in the axial plane as three parallel lines: the falx cerebri and the medial borders of the two hemispheres. However, at the time of midtrimester ultrasound screening, indirect signs may be either absent or barely visible but may appear more clearly later in gestation. In a sagittal view, ACC results in an abnormal induction of the medial cerebral convolutions, leading to a radial arrangement of the sulci, strengthened by the hypoplasia or absence of the cingulate gyrus. By colour-flow Doppler, the pericallosal arteries display an irregular radiant vascular pattern ( Figs. 28.24 and 28.25 ).

Indirect sonographic signs suggesting complete absence of the corpus callosum. A, Colpocephaly with a teardrop-shaped lateral ventricle. B, Three-layer sign.

Abnormal irregular radial vascularisation pattern of the pericallosal artery in complete absence of the corpus callosum.

Sagittal T2 HASTE image of the brain in a fetus at 31 weeks. Absence of the corpus callosum with visualisation of the fornices (circle) and typical sunburst radiation of the gyri.

Partial Agenesis of the Corpus Callosum

In partial ACC, the CSP is usually present but is abnormally shaped. Only the midsagittal views of the fetal brain allows for the differentiation among complete agenesis, hypoplasia or partial formation of the CC ( Fig. 28.26 ). In hypoplasia of the CC, often the posterior portion is affected. Only a handful of cases have been detected prenatally.

Partial agenesis of the corpus callosum: the rostrum and genu are absent (arrowhead) . Note the presence of a well-developed cavum septi pellucidi (asterisk) .

The pericallosal artery follows the anterior part of the CC but loses its normal course posteriorly.

Absence of the Cavum Septi Pellucidi

Absence of the CSP occurs in about 0.2 to 0.3 per 10,000 pregnancies. The CSP appears as a fluid-filled box on an axial plane between the frontal horns, the CC and the thalami. In a sagittal plane, it is localised under the anterior part of the CC. The CSP is square in 73% and triangular in 27%; however, in cases with CV, the appearance is rectangular. The mean width at midtrimester is 3.4 mm. The CSP progressively decreases in size from 26 weeks of gestation. By term, the closure of the CSP is seen in 97% of fetuses, although occasionally, this cavity remains open until adulthood. Failure to visualise the CSP between 18 and 37 weeks is highly indicative of cerebral anomalies. Although it may occur as a normal variant if isolated, absence may be associated with the HPE spectrum, septo-optic dysplasia (SOD), callosal dysgenesis and hypogenesis, chronic severe hydrocephalus resulting from aqueductal stenosis or CM, schizencephaly, porencephaly or hydranencephaly and basilar encephaloceles. Genetic causes are rare. The persistence of an enlarged CSP (>1cm) beyond infancy has been associated with cerebral dysgenesis.

Septo-Optic Dysplasia

Septo-optic dysplasia can be suspected when the CSP is absent in an otherwise normal brain ( Fig. 28.27 ). The frontal horns are fused at the midline, and the CC is frequently thin. VM can be present. In experienced hands, sonographic 3D visualisation and measurement of the chiasma and optic nerves may confirm the diagnosis. Fetal MRI is generally more suited to exclude optic tract hypoplasia. Additional endocrinologic evaluation and visual assessment are mandatory to differentiate from isolated absent CSP. The prognosis of an isolated absent CSP is usually good. In nonisolated cases, the prognosis is related to the associated conditions. The recurrence risk for isolated absent CSP is low, but in a few cases, Mendelian inheritance is suggested.

Fusion of the anterior horns and absence of the septum pellucidum has been observed as an isolated finding in association with optic atrophy in septo-optic dysplasia and in the presence of lobar holoprosencephaly.

Introduction

By the fifth or sixth gestational week, the pontine flexure creates the plica choroidea and divides the rhombencephalon into the metencephalon and the myelencephalon. Invagination divides the roof of the fourth ventricle into an anterior and a posterior membranous area. The anterior membranous area gives rise to the cerebellar vermis. Cerebellar vermian growth forces the posterior membranous area of the roof of the fourth ventricle to invaginate posteriorly below the vermis, resulting in the Blake pouch. The median fenestration of the Blake pouch by the foramen of Magendie leads to its subsequent disappearance. The foramina of Luschka open later, around the fourth month. In 1% to 2% of healthy subjects, the foramen of Magendie is absent; the communication between the fourth ventricle and the subarachnoid space is established when the foramina of Luschka open. The cerebellum results from the development of two lateral primordia that fuse subsequently across the midline to form the vermis, starting at the end of the sixth week. At the 11th week, the cerebellum covers the fourth ventricle and subsequently starts subdividing into fissures directed perpendicularly to the longitudinal axis of the brainstem. The development of the cerebellar cortex results in the formation of folia.

Routine sonographic evaluation of the posterior fossa occurs in the axial suboccipital bregmatic view, displaying the two cerebellar hemispheres connected with the vermis and the cisterna magna as the space between the vermis and the inner layer of the occipital bone. The cerebellum appears as a butterfly-shaped structure formed by the round cerebellar hemispheres joined in the middle by the slightly more echogenic cerebellar vermis. The cerebellar hemispheres are well depicted on transverse and coronal images and are hypoechoic with a more echogenic lining. By the end of the second trimester, the increased development of the folia leads to an increased echogenicity characterising the striped appearance. Two retrocerebellar septa, perpendicular to the cerebellum, can be visualised in a transverse view in the cisterna magna in the second and third trimesters in 84% to 92% of fetuses, respectively, and are considered to be remnants of the walls of the Blake pouch. A more detailed examination of the vermis can be performed using the midsagittal plane depicting the triangular fourth ventricle (fastigium), the pons, the posterior fossa fluid space and the tentorium cerebelli. The vermis appears markedly hyperechoic, and the primary fissure is constantly observed on the midsagittal image from 24 weeks’ gestation as a transverse more echoic line. Reliable interpretation of the normal development and growth of the cerebellar hemispheres and vermis is possible from 18 weeks onwards.

Dandy-Walker Complex

Posterior fossa malformations have recently been grouped as the Dandy-Walker continuum because of new insights in the embryologic development of this region. This continuum includes isolated enlarged cisterna magna, the Blake pouch cyst, vermian hypoplasia and the Dandy-Walker malformation (DWM). The sonographic categorisation of posterior fossa fluid collections depends on the assessment of the position of the torcular and the integrity of the cerebellar vermis. Pitfalls in the diagnosis of posterior fossa anomalies have been attributed to confusion in terminology describing vermian pathology, the gestational age at diagnosis, the incorrect assessment of the midsagittal plane of the cerebellum and the late development of some pathological conditions. More detailed examination by transvaginal ultrasound includes the proper identification of the fastigium and its relation to the vermis by assessment of the angle between vermis or brainstem and tentorium and the appearance of the primary fissure. Multiplanar imaging of a standard 3D volume and the use of tomographic ultrasound imaging or VCI (volume contrast imaging) facilitates the visualisation and biometry of the midsagittal structures of the posterior fossa, especially the vermis and the fastigium.

Fetal MRI offers a clearer view of the torcular, and the assessment of the integrity of the vermis remains difficult particularly in midgestation. Current fetal MRI, particularly in early gestation before 24 gestational weeks, has limitations in accurately predicting postnatal MRI abnormalities. In 41%, fetal and postnatal MRI diagnoses disagree; postnatal MRI reversed fetal MRI diagnoses in 15% and revealed additional anomalies in 26%. MRI in early gestation (before 18 weeks), although presumed safe, results in a higher false-positive rate because of fetal motion, small anatomic structures (limited spatial and tissue resolution) and rapid growth of the cerebellum later in pregnancy (second and third trimesters). T2-weighted images provide structural information and can be complemented with T1-weighted and echo planar imaging to detect haemorrhage. Normative charts of the posterior fossa and its structures are available.

Isolated Mega Cisterna Magna

The cisterna magna is a fluid-filled space posterior to the cerebellum. In the second half of gestation, the anteroposterior diameter of the cisterna magna is stable and measures between 2 and 10 mm. Early in gestation as the cerebellar vermis does not completely cover the fourth ventricle, it may give the false impression of a defect of the vermis. A CM of more than 10 mm without associated anomalies suggests the diagnosis of isolated mega cisterna magna (MCM).

Isolated MCM is defined as a distance between the vermis of the cerebellum and the inner border of the occipital bone of more than 10 mm on an axial plane through the CSP and the vermis. The vermis is intact, the fourth ventricle is normal and there is no VM nor displacement of the torcular. The prevalence is estimated at 2%. Isolated MCM is usually an incidental finding and may be secondary to a temporary distention of the Blake pouch without displacement of the vermis.

The condition should be differentiated from the Dandy-Walker complex, cerebellar hypoplasia and posterior fossa arachnoid cyst.

Adults with isolated MCM have normal cognitive function but with reduced memory and verbal fluency. Children with an enlarged cisterna magna are at risk for mild developmental delay. Most studies report a good prognosis. The non-isolated cases of MCM have abnormal developmental function in 11% to 29% of cases. In syndromic conditions, the prognosis depends on the underlying condition.

Blake Pouch Cyst

If the Blake pouch fails to perforate to form the midline aperture of the foramen of Magendie, the accumulation of CSF results in a cystlike structure projecting into the cisterna magna. The Blake pouch cyst remains in communication with the fourth ventricle. The position of the tentorium cerebelli is intact, but an upward and posterior rotation (<45 degrees) of a normally developed vermis with a normal cisterna magna is characteristic of a Blake pouch cyst. On an axial oblique plane, such a Blake pouch cyst may be misinterpreted as partial vermian agenesis ( Fig. 28.28 ). The diagnosis can be made in the second trimester of pregnancy. Differential diagnosis with inferior vermian hypoplasia remains difficult even with the help of prenatal MRI. The fluid content of the Blake pouch cyst shows a more translucent echogenicity than that of the cisterna magna. On fetal MRI, the same findings will be visible, most evident in the sagittal plane, with a complete but rotated vermis, normal torcular herophili and a large cyst in communication with the fourth ventricle.

Blake pouch cyst. A, Axial view of the posterior fossa, revealing a cystic structure in association with the cerebellum. B, Sagittal imaging allows easy differentiation form other posterior fossa anomalies ( asterisk indicates the upward-rotated vermis; ° indicates Blake pouch).

The overall neurologic outcome of Blake pouch cyst is good because the cerebellum and vermis have developed completely. A delayed fenestration between 24 and 26 weeks’ gestation may occur in 50% of cases. In case of secondary VM, postnatal ventriculoperitoneal shunting is mandatory. In a retrospective evaluation of 19 cases of Blake pouch cyst, 10 fetuses presented without associated malformations, 7 of which presented a normal outcome. In 4 cases of the 10, a late fenestration occurred. Nine cases of 19 showed additional malformations: 5 of 9 had a cardiac anomaly, 1 of which had trisomy 21. The recurrence risk is low.

Dandy-Walker Malformation

Dandy-Walker malformation ranges from 1 in 25,000 to 1 in 35,000 live births to 1 in 5000 and is characterised by the absence or severe dysplasia of the cerebellar vermis, a cystic enlargement of the posterior fossa in communication with the fourth ventricle and an upward displacement of the tentorium cerebelli. This condition is often associated with other CNS anomalies (in 50%–60% of cases): the VM(36%–67%), agenesis of the CC (5%–50%) and HPE. Associations with congenital heart defects, urinary tract anomalies and facial clefts have been described, often in the context of chromosomal anomalies (50%–70% of the cases: T13, T18, T21, 45,X) and genetic syndromes(Walker-Warburg syndrome, Aicardi syndrome, Neu-Laxova syndrome and Meckel-Gruber syndrome). Maternal diabetes, excessive alcohol consumption and early in utero infection may predispose to the condition.

On ultrasound, DWM is characterised by a large communication between ‘the fourth ventricle’ and the cisterna magna, without clear visualisation of the vermis on the axial transcerebellar section. On sagittal imaging, the vermis is absent or severely hypoplastic, rotated counterclockwise and positioned behind the quadrigeminal plate. The tentorium cerebelli is elevated by an infratentorial cyst increasing the angle between the brainstem and tentorium to more than 40 degrees. VM is present in 68% of the cases despite the absence of associated malformations or an abnormal karyotype. Prenatal array CGH and in particular the exclusion of subtelomeric deletions (e.g., 6p) is recommended.

Fetal MRI provides detailed information about neuroanatomy and can identify additional malformations, such as brainstem abnormalities, heterotopia or abnormal gyration, which are typically hard to find on ultrasound. MRI improves the diagnostic accuracy up to 88% compared with 65% for antenatal ultrasound ( Fig. 28.29 ). The overall effect of the fetal MRI on clinical management is significant in 35% of cases. Developmental delay, including hypotonia, cerebellar dysfunction and hemiparesis have been reported in 40% to 60% of children with DWM. The outcome is extremely variable ranging from severely delayed motor development (30.4%), hypotonia, ataxia and seizures. Intellectual development is normal in 35% to 50% of the cases depending on the vermian development and absence of supratentorial malformations. Partial agenesis of the vermis with a normal or almost normal lobulation, although difficult to evaluate because of the mass effect of the posterior fossa cyst, has a better prognosis. The recurrence rate in nonsyndromic DWM is sporadic (1%–5%); in case of chromosomal anomalies, it is less than 1% and in syndromic forms (e.g., Walker-Warburg, Meckel-Gruber, Leu-Laxova syndromes) up to 25%.

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