Sonography of the Fetal Central Nervous System

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.

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 ).

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.

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 ).

Iniencephaly

The aetiology of this lethal condition is unknown. Iniencephaly is a combination of a deficient occiput and inion, a rachischisis of the cervicothoracic spine and an extreme retroflexion of the head.

Sonographic appearance showed a fixed flexion of the head with an upturned face (stargazer appearance). Cervical and thoracic vertebrae show incomplete formation or closure; the occipital bones seem fused with the cervicothoracic vertebrae. Associated anomalies have been reported in more than 80% of cases.

Iniencephaly should be distinguished from extreme hyperextension of the fetal head, which may resolve spontaneously, and Klippel-Feil syndrome. Because of the hyperextension of the head, dystocia may occur. Early induction of labour should be considered to avoid Caesarean section.

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.

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.

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.

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 .

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 ).

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.

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 ).

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.

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

Corpus Callosum Dysgenesis

A thick CC is identified in 5% of CC abnormalities. It can be associated with macrocephaly, macrocephaly-capillary syndrome and Cohen syndrome.

Hyperechogenicity of the CC is characteristic of pericallosal lipoma which is often isolated. Sometimes it is part of a frontonasal dysplasia, Goldenhar syndrome or Pai syndrome. Because of the association with chromosomal abnormalities of various kinds, array CGH is highly recommended. In addition to the fetal neurosonogram, a detailed examination of all fetal organ systems, especially the fetal heart, the genitourinary system and the skeleton, should be performed.

The identification by means of fetal MRI of more discrete CNS lesion (≤22.5%) such as abnormal gyration, heterotopia and migration anomalies in association with CCA enables refinement of the diagnosis and prognosis. MR is less accurate in measuring thickness of the CC because of the low spatial resolution of MRI. Subjective callosal thickening should alert the specialist, and additional abnormalities should be looked for. In addition, new MRI techniques such as fibre tracking and functional MRI may help to differentiate isolated cases with usually a good prognosis from those with additional cerebral lesions and an adverse outcome.

Neurologic Outcome

Significant neurodevelopmental delay may occur in 15% to 36% of the cases of isolated CCA. The presence of other cerebral and extracerebral malformations worsens the neurodevelopmental outcome. A systematic review assessing the of neurodevelopmental outcome in 132 fetuses revealed a normal outcome in 74.3% with complete CCA and in 65.5% of partial CCA. Moderate and severe disability was reported in 14.3% and 11.4% of CCA and in 6.9% and 27.6% of partial CCA, respectively. Subtle perceptual, neuropsychological and motor defects may arise later in life.

Of major importance, an additional 15% of prenatally isolated ACC cases were found to have associated problems after birth. At the age of 10 years, 75% of the children have a normal intelligence but frequently with mild learning difficulties.