**4. Neural tube defects**

Neural tube defects (NTDs) are a frequent group of severe anomalies of the central nervous system. The most frequent conditions are anencephaly, spina bifida, and cephalocele [15]. The open NTDs occur as a result of a primary failure of the neural tube closure between the 17th and 30th postfertilization days. They have a rather stable prevalence. This highlights the importance of primary prevention by folic acid supplementation and the paramount meaning of accurate prenatal diagnosis. In rare cases, some forms of NTDs may be recognized very early in pregnancy (**Figure 16**).

2D planes and markers for fetal central nervous system (CNS) morphologic assessment at the first-trimester ultrasound scan are shown in **Figure 17**: left column, a normal fetus; right

Fetal Central Nervous System Abnormalities http://dx.doi.org/10.5772/intechopen.76208 53

In the thalamic plane, the regularity of the skull and the bone ossification should be assessed. Also, measurements may be performed: the biparietal diameter (BPD), the head circumference (HC), and optional—the occipito-frontal diameter (OFD). Thalamus, the third ventricle (red arrow), and symmetry of the intracranial structures may be subjectively assessed. In this plane, the "crash sign" may be subjectively evaluated (the aqueduct of Sylvius position) or the distance between this feature and the occipital bone may be measured (the aqueduct—indicated by the blue quadrant, and

In the lateral third-ventricle plane, aside from the regularity of the skull and the bone ossification assessment, the following structures should be visualized: the midline falx echo, the choroid plexuses, the interhemispheric fissure, the posterior horns of the lateral ventricles (LVs), the lateral walls of the anterior horns of the LV, and the thin brain mantle. In this plane, the "dry brain phenomenon" is usually present in OSB cases: the subjective large choroid plexus

In the sagittal plane (often called the *mid-sagittal* plane), many CNS structures may be identified and measured: the thalamus (T), the brain stem (BS), the medulla oblongata (MO), the midbrain (M), and the future cisterna magna (CM). In OSB cases, some mild signs may be found: the alteration of the BS (brainstem diameter)/BSOS (brainstem to occipital bone diameter) ratio and the decreased frontomaxillary facial (FMF) angle. The most valuable in screen-

Along with the mild early signs of spinal neural tube defects, other major malformations reach 100% detection rates in many reports. **Figures 20**–**22** show several such cases, showing

mesencephalon—normal by the yellow contour and pathologic by the red contour).

ing seems to be the alteration of the cisterna magna (**Figure 19**).

correlations between the ultrasound data and the specimen aspects.

**Figure 17.** The transthalamic view of cranium in a normal (left) and an OSB case (right).

**Figure 18.** The sagittal plane of cranium in a normal (left) and an OSB case (right).

column, isolated OSB fetus.

for the skull (**Figure 18**).

Yet, the vast majority of cases are approached in the late first trimester (11–13 WA), due to the fact that the role of this scan has evolved [5, 7, 8, 16–18]. The technique has grown, no longer being a screening for aneuploidy tool [19–22]—but a method to almost assess the complete fetal anatomy. This became the first anomaly scan in many units [4, 5, 18, 23–25].

In terms of central nervous system, the newest area of debate is the significance of posterior fossa ultrasound semiology. At 11–14 weeks of gestation, it is possible to visualize and measure many spaces in the posterior brain: the brainstem (BS), the fourth ventricle or intracranial translucency (IT), and the cisterna magna (CM). In some settings, such anatomical spaces are assessed routinely by ultrasound in parasagittal or oblique views of the fetal face, as part of the nuchal translucency (NT) scan [26, 27]. Abnormalities of the posterior brain spaces or deviations of their measurements have been proposed as markers of congenital malformations of the posterior fossa [26–29]. Subsequently, the correlation between the decreased amount of intracranial fluid and open spina bifida (OSB) has been established [16, 30]. More recently, it has been suggested that increased fluid may indicate the presence of cystic posterior fossa anomalies such as Dandy-Walker malformation (DWM) and Blake's pouch cyst (BPC) [31–35].

Also, the axial planes offer many indirect signs of OSB and have competed with the sagittal planes in the efficacy of first-trimester screening for OSB [36–38]. It seems that in experienced hands, OSB may reach 100% early detection rates, being reliably diagnosed at 11–14 weeks of screening [39].

In our view, both sagittal and axial planes of the fetal head may be used in OSB screening, depending on the operator's skills and the equipment used. Also, the small BPD may be useful [40, 41].

**Figure 16.** Early embryonic demise, in a case of suspected exencephaly.

2D planes and markers for fetal central nervous system (CNS) morphologic assessment at the first-trimester ultrasound scan are shown in **Figure 17**: left column, a normal fetus; right column, isolated OSB fetus.

**4. Neural tube defects**

52 Congenital Anomalies - From the Embryo to the Neonate

early in pregnancy (**Figure 16**).

23–25].

(BPC) [31–35].

screening [39].

ful [40, 41].

Neural tube defects (NTDs) are a frequent group of severe anomalies of the central nervous system. The most frequent conditions are anencephaly, spina bifida, and cephalocele [15]. The open NTDs occur as a result of a primary failure of the neural tube closure between the 17th and 30th postfertilization days. They have a rather stable prevalence. This highlights the importance of primary prevention by folic acid supplementation and the paramount meaning of accurate prenatal diagnosis. In rare cases, some forms of NTDs may be recognized very

Yet, the vast majority of cases are approached in the late first trimester (11–13 WA), due to the fact that the role of this scan has evolved [5, 7, 8, 16–18]. The technique has grown, no longer being a screening for aneuploidy tool [19–22]—but a method to almost assess the complete fetal anatomy. This became the first anomaly scan in many units [4, 5, 18,

In terms of central nervous system, the newest area of debate is the significance of posterior fossa ultrasound semiology. At 11–14 weeks of gestation, it is possible to visualize and measure many spaces in the posterior brain: the brainstem (BS), the fourth ventricle or intracranial translucency (IT), and the cisterna magna (CM). In some settings, such anatomical spaces are assessed routinely by ultrasound in parasagittal or oblique views of the fetal face, as part of the nuchal translucency (NT) scan [26, 27]. Abnormalities of the posterior brain spaces or deviations of their measurements have been proposed as markers of congenital malformations of the posterior fossa [26–29]. Subsequently, the correlation between the decreased amount of intracranial fluid and open spina bifida (OSB) has been established [16, 30]. More recently, it has been suggested that increased fluid may indicate the presence of cystic posterior fossa anomalies such as Dandy-Walker malformation (DWM) and Blake's pouch cyst

Also, the axial planes offer many indirect signs of OSB and have competed with the sagittal planes in the efficacy of first-trimester screening for OSB [36–38]. It seems that in experienced hands, OSB may reach 100% early detection rates, being reliably diagnosed at 11–14 weeks of

In our view, both sagittal and axial planes of the fetal head may be used in OSB screening, depending on the operator's skills and the equipment used. Also, the small BPD may be use-

**Figure 16.** Early embryonic demise, in a case of suspected exencephaly.

In the thalamic plane, the regularity of the skull and the bone ossification should be assessed. Also, measurements may be performed: the biparietal diameter (BPD), the head circumference (HC), and optional—the occipito-frontal diameter (OFD). Thalamus, the third ventricle (red arrow), and symmetry of the intracranial structures may be subjectively assessed. In this plane, the "crash sign" may be subjectively evaluated (the aqueduct of Sylvius position) or the distance between this feature and the occipital bone may be measured (the aqueduct—indicated by the blue quadrant, and mesencephalon—normal by the yellow contour and pathologic by the red contour).

In the lateral third-ventricle plane, aside from the regularity of the skull and the bone ossification assessment, the following structures should be visualized: the midline falx echo, the choroid plexuses, the interhemispheric fissure, the posterior horns of the lateral ventricles (LVs), the lateral walls of the anterior horns of the LV, and the thin brain mantle. In this plane, the "dry brain phenomenon" is usually present in OSB cases: the subjective large choroid plexus for the skull (**Figure 18**).

In the sagittal plane (often called the *mid-sagittal* plane), many CNS structures may be identified and measured: the thalamus (T), the brain stem (BS), the medulla oblongata (MO), the midbrain (M), and the future cisterna magna (CM). In OSB cases, some mild signs may be found: the alteration of the BS (brainstem diameter)/BSOS (brainstem to occipital bone diameter) ratio and the decreased frontomaxillary facial (FMF) angle. The most valuable in screening seems to be the alteration of the cisterna magna (**Figure 19**).

Along with the mild early signs of spinal neural tube defects, other major malformations reach 100% detection rates in many reports. **Figures 20**–**22** show several such cases, showing correlations between the ultrasound data and the specimen aspects.

**Figure 17.** The transthalamic view of cranium in a normal (left) and an OSB case (right).

**Figure 18.** The sagittal plane of cranium in a normal (left) and an OSB case (right).

**5. Cortical formation abnormalities**

a destructive process mediated by vascular injury also.

abnormalities.

[44–50].

[52] (**Figure 23**).

The cerebral *cortex development* implies evolvement through three steps: neuronal precursor proliferation and differentiation; migration of immature neurons; and cortical maturation (the laminar organization and occurrence of synapsis). Neurons migrate from the ventricular zone (called the germinal matrix) toward the pial surface, along radially oriented glial scaffolds [42–44]. Gyration and sulcation occur afterword, beyond 32 WA. Disruption of any of these steps in cerebral development, due to inherited or acquired causes, can result in a wide spectrum of

Fetal Central Nervous System Abnormalities http://dx.doi.org/10.5772/intechopen.76208 55

*Schizencephaly* is a congenital cerebral defect in clefting, where clefts extend through the hemispheres from the ventricles to the pial surface [45]. Having two clinical types (open and closed), it seems to be caused by a primary failure of development of the cerebral mantle in early pregnancy. The condition is different from *porencephaly*, being characterized by the presence of heterotopic gray matter lining the cleft. Although primary, it has also been reported as

*Lissencephaly* means literally "smooth brain." This is a rare brain malformation, gene-linked, characterized by the absence of normal convolutions in the cerebral cortex, leading to *microcephaly*. In most cases, neonates have usually a normal sized head at birth. The "cobblestone lissencephaly" is characterized by the irregular surface of the brain on the pathological specimen. This is due to aberrant neuroglial overmigration into the subarachnoid space. The formation of an extracortical agyric neuroglial layer occurs. It seems that the primary cause is the deficit of glycosylation of dystroglycans, resulting in neuroglial overmigration

The presence of neurons in any position other than the cortex is called *neuronal heterotopia*. This is caused by an abnormal phenomenon of migration during fetal development. The most frequent type is *periventricular* heterotopia, given by an abnormal development of the neuroependyma [44, 50]. It consists of groups of disorganized neurons and glial cells that are located along the walls of the lateral ventricles. They may be isolated (X-linked and non-X-linked forms) or associated with other CNS malformations. The prevalence in the general population is unknown, but it has been related with epilepsy, seizures, and/ or developmental delay, with different grades of severity. The prenatal diagnosis has been reported, but the condition is underdiagnosed in the vast majority of screening settings. The true *microcephaly* is considered part of a complex disorder [48–51], occurring in syndromes (with or without chromosomal anomalies). It may be associated exclusively with cerebral anomalies (due to either primary cerebral maldevelopment or clastic events like the ischemohemorrhagic ones) or infectious diseases; the latter has gained a particular interest lately, in light of the recent emergence of microcephaly related to Zika virus infection [48–51]. *Macrocephaly* may result from macrocrania, hydrocephalus, or a major subarachnoid space abnormality. If not associated with other conditions, macrocephaly is synonymous with megalencephaly, meaning an increase in the weight and size of the brain

**Figure 19.** Rachischisis. Medical termination of pregnancy at 16 WA. 3D ultrasound in a surface-rendering mode (a), pathologic specimen (schisis of the lumbar skin, with exposing the meninges and the spinal canal structures) and MRI details of specimen, confirming the hemivertebra suspected on US.

**Figure 20.** Exencephaly. Ultrasound images and the pathologic specimen at 12 WA.

**Figure 21.** Encephalocele at 12 W. Conventional 2D ultrasound and 3D surface rendering.

**Figure 22.** Complex lethal facial and cerebral anomaly. The red arrow indicates the single orbit. The pathologic specimen confirms ciclopy, proboscis, exencephaly (a). Second-trimester case of anencephaly: 2D conventional and 3D ultrasound (b).
