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Midline cerebral anomalies include a group of brain defects that encompass a wide spectrum of severity and are typically associated with craniofacial malformations.
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The holoprosencephalies are complex abnormalities of the forebrain that share in common an incomplete separation of the cerebral hemispheres and formation of diencephalic structures.36 The most widely accepted classification of these disorders (Figure 15-16) recognizes 4 major varieties: the alobar, semilobar, and lobar types, plus the more recently described middle interhemispheric variant. In the alobar variety, the most pronounced type, the interhemispheric fissure and the falx cerebrii are totally absent, there is a single primitive ventricle (holoventricle), the thalami are fused on the midline, and there is absence of the third ventricle, neurohypophysis, olfactory bulbs, and tracts. In semilobar holoprosencephaly, the 2 cerebral hemispheres are partially separated posteriorly, but there is still a single ventricular cavity. In both the alobar and semilobar forms, the roof of the ventricular cavity, the thela choroidea, normally enfolded within the brain, may balloon out between the cerebral convexity and the skull to form a cyst of variable size—the dorsal sac. Alobar and semilobar holoprosencephaly are often associated with microcephaly, and less frequently with macrocephaly, which is invariably due to internal obstructive hydrocephalus. In the lobar variety, the interhemispheric fissure is well developed posteriorly and anteriorly, but there is still a variable degree of fusion of the cyngulate gyrus and of the lateral ventricles, and absence of the septum pellucidum. In the middle interhemspheric variant of holoprosencephaly, fusion occurs mostly at the level of the bodies of lateral ventricles, while the frontal horns and posterior horns are relatively well developed.37
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Alobar and semilobar holoprosencephaly are typically and almost constantly associated with facial anomalies that can be regarded as the consequence of hypoplasia of the midfacial structures. The malformations span between cyclopia and severe hypotelorism with median cleft lip–palate. The nose can be absent, replaced by a proboscis, or be extremely flattened.36 Conversely, facial anomalies are rarely encountered in the lobar form and middle interhemispheric variant.
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Holoprosencephaly at birth is exceedingly rare. This anomaly has a high intrauterine fatality rate and is infrequently encountered in prenatal studies. The etiology is heterogeneous. In most cases, the anomaly is isolated and sporadic. In other cases, chromosomal abnormalities have been found (trisomy 13 and polyploidy) and/or anatomic abnormalities are found.
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Prenatal diagnosis of alobar holoprosencephaly depends upon the demonstration of a single rudimentary cerebral ventricle that may protrude posteriorly through the incompletely enfolded cortex to form a dorsal sac (Figure 15-17). Additional findings include the presence of typical facial anomalies. Similar findings are expected with the semilobar type. The middle interhemispheric variant of alobar holoprosencephaly is characterized by relatively well-formed frontal horns that are fused on the midline without intervening septum pellucidum, and communicate posteriorly with a single rudimentary cavity (Figure 15-18). Recognition of the lobar variety has also been reported, although the differentiation from other cerebral anomalies such as the simple agenesis of the septum pellucidum is always difficult. This condition may be suspected in axial views, mainly because of an absent septum pellucidum with ventriculomegaly. However, the coronal scan is most informative because it demonstrates the flat, squared roof of the frontal horns, as well as an ample inferior communication with the inferior third ventricle. The presence of fused fornices, which appear as a linear structure running within the third ventricle from the anterior to the posterior commissure, is a frequent and very specific finding with this condition (Figure 15-19).38,39
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The invariably poor prognosis for infants affected by alobar and semilobar holoprosencephaly is well established. Thus far, cases diagnosed in utero with lobar holoprosencephaly also had extremely poor neurologic development.38,40
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Agenesis of the corpus callosum (ACC) is an anomaly of uncertain prevalence and clinical significance. Estimates of 0.3% to 0.7% in the general population and 2% to 3% in the developmentally disabled are usually quoted. The etiology is heterogeneous. Genetic factors are probably predominant. The high frequency of associated malformations and chromosomal aberrations suggest that ACC is often part of a widespread developmental disturbance.
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Agenesis of the corpus callosum may be either complete or partial. In the latter case, also referred to as dysgenesis of the corpus callosum, the caudad portion (splenium and body) is missing to varying degrees.
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The diagnosis of agenesis of the corpus callosum is possible from midgestation41 but is a challenge even for expert sonologists.42 With complete agenesis of the corpus callosum there is no septum pellucidum, the 2 hemispheres tend to be more separated than usual in the central part of the brain, and there are typical modifications in the morphology of the lateral ventricle. In the coronal section, the frontal horns are more distant than usual and have a "comma" shape, while in the transverse plane the lateral ventricle has a "teardrop" shape that is due to the combination of the posterior enlargement of the atria and occipital horn with frontal horns that have a normal size but are more separated than usual. In routine examinations an increased atrial width with a typical "teardrop configuration" of the lateral ventricles and/or failure to visualize the cavum septum pellucidum should alert the possibility of fetal ACC. Once a suspicion has been formulated, a direct diagnosis is possible by demonstrating the absence of the corpus callosum by coronal and sagittal scans (Figure 15-20).
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Diagnosis of partial ACC has also been reported, but the sonographic findings are even more elusive than with the complete form (Figure 15-21).41,43 The cavum septi pellucidi are usually present and the axial sections may be completely unremarkable. Identification of partial ACC requires a median section demonstrating that the posterior portion of the corpus callosum is absent. This results in the corpus callosum forming an incomplete arch over the area of the fourth ventricle. The incomplete corpus callosum also tends to be thinner and to form an angle that is more open posteriorly than usual.
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Agenesis of the corpus callosum, be it complete or partial, is frequently part of a syndrome or is associated with multiple malformations (Table 15-2). As an isolated finding, ACC is usually associated with normal to borderline intellectual development.41,44 However, long-term studies have reported a progressive decrease in intellectual capacity throughout the years, and most infants tend to have significant difficulties in school.45 Agenesis of the corpus callosum has also been linked to psychosis.46
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Absence of the septum pellucidum is present with holoprosencephaly and agenesis of the corpus callosum. It may also occur with other intracranial anomalies, such as de Morsier syndrome or septooptic dysplasia, cortical abnormalities, and schizencephaly, or it may also be present as an isolated finding (Figure 15-22).37,47,48, and 49 The differential diagnosis is frequently difficult. Pediatric data suggest, however, that the prognosis is often severe, with more than 90% of cases demonstrating mental retardation and/or severe neurologic abnormalities.49
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The term Dandy-Walker syndrome or malformation was originally introduced to indicate the association of (1) ventriculomegaly of variable degree; (2) a fourth ventricle that is posteriorly open, causing superior displacement a large cisterna magna; and (3) a defect in the cerebellar vermis through which the cyst communicates with the fourth ventricle. In these cases, the axial plane demonstrates a large cisterna magna and a median V-shaped defect of the cerebellum that extends into the fourth ventricle. In the median plane, which is the most important one for the diagnosis, the cisterma magna extends superiorly, displacing the cerebellar vermis (which is frequently hypoplastic) and elevating above its normal position the tentorium cerebelli and the torcular herophili (Figure 15-23). The presence of ventriculomegaly is not essential to make the diagnosis because in many cases it has been found to develop only years after birth. Dandy-Walker malformation is frequently associated with other neural defects, mostly with other midline anomalies, such as agenesis of the corpus callosum and holoprosencephaly. Other deformities include encephaloceles, polycystic kidneys, cardiovascular defects, and facial clefting. Table 15-3 lists the most frequent associations. Even if isolated, it has been generally considered to have a poor prognosis. However, recent experience with magnetic resonance (MR) in infants suggests that those cases in which the vermis appears hypoplastic have a subnormal intelligence in 85% of cases versus only 15% of those in which the vermis appears intact.50,51 In the original study, the cerebellar vermis was considered normal if it was possible with MR to document in the median plane 3 main anatomic landmarks: the fastigium point that corresponds to the posterior apex of the fourth ventricle and the 2 main fissures. A similar approach has also been suggested for antenatal studies. Both MR and multiplanar, possibly transvaginal, ultrasonography can be used. It is expected, however, that the small size of the vermis and the difficulty in obtaining an exact median plane will represent at times major limiting factors, particularly in early gestation.
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Dandy-Walker malformation is exceedingly rare, with an estimated incidence of about 1:30,000 births, and is found in 4% to 12% of all cases of infantile hydrocephalus. However, minor variations of this condition are rather frequently encountered, as it is attested by an increasing number of reports, both in the prenatal and pediatric literature. The term Dandy-Walker complex (or continuum) is used to indicate this spectrum of abnormal findings that share in common an enlargement of the cisterna magna and/or the impression of a V-shaped cleft in the cerebellar vermis in the axial plane.50,52,53
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The Dandy-Walker complex is very frequently a part of multiple anomalies or syndromes (see Table 15-3), and it is always difficult to predict the outcome for a given fetus. When other anomalies are excluded, however, careful evaluation of the posterior fossa anatomy may orient the prognosis. If the cisterna magna depth is 10 mm and the cerebellar vermis appears intact and in its normal position, the condition is usually referred to as megacisterna magna (Figure 15-24). Although this is a risk factor for associated malformations including aneuploidies (trisomy 18 in particular)54,55 most isolated cases are of no consequence.8,33,52,56 If there is the impression of a V-shaped cleft in the cerebellum in the axial plane and the median plane reveals a vermis that is intact, the diagnosis is most likely a Blake pouch cyst (Figure 15-25), and the prognosis is usually good.33,57 Conversely, a hypoplastic superiorly rotated vermis is the landmark of vermian hypoplasia (Figure 15-26), previously referred to as Dandy-Walker variant, a condition that is frequently associated with other intracranial anaomalies and carries a very high risk of abnormal neurodevelopment.50,51, and 52 Distinction between an intact and a hypoplastic vermis is far from simple. Under normal conditions, in the median plane it is usually possible with either sonography or MR to demonstrate the fastigium of the fourth ventricle and the 2 main fissures from about midgestation.50,51, and 52 With hypoplasia of the vermis these landmarks cannot be identified. Nomograms of the normal size of the vermis throughout gestation are also available (Table 15-4).58
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In our own experience, isolated megacisterna magna and Blake pouch cyst represent the bulk of the posterior fossa anomalies that are diagnosed antenatally.8 Although the available data are limited and the neurologic risk cannot be predicted precisely, it would seem that prognosis is usually good.
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The greatest diagnostic challenge is probably represented by Joubert syndrome, an anomaly with autosomal recesive transmission that is featured by absence or hypoplasia of the vermis, which, however, is not rotated. In a pregnancy at specific risk, the condition can be suspected when a communication is seen between the fourth ventricle and a cisterna magna of normal size in the transverse plane.59 In the absence of the vermis, the 2 hemispheres impinge on the midline, and therefore the median plane is of little use, although at times it may demonstrate a fourth ventricle of slightly irregular shape.59 In the absence of a positive familial history, however, this finding has a very low predictive value and most cases that we have seen were found to be normal at birth.
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Caution is warranted while making the diagnosis of a minor variety of the Dandy-Walker continuum. Development of the cerebellar vermis is incomplete prior to 20 weeks' gestation and this frequently creates an artifact mimicking a vermian defect.60
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In general, meticulous scanning with a multiplanar approach is recommended in cases with a suspicion of a posterior fossa anomaly. The poor correlation that has been demonstrated in several studies between antenatal diagnosis and autopsy finding is probably related to the use of only axial planes, which can be extremely misleading. In the axial plane, entities that are clinically different, such as Dandy-Walker malformation, vermian hypoplasia, and Blake pouch cyst, cannot be clearly differentiated.
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As the diagnosis of midline anomalies depends upon section planes of the fetal head that are sometimes difficult to obtain, we have found that three-dimensional ultrasound is frequently of considerable help. Multiplanar slicing of a volume obtained from axial scans usually provide images of diagnostic quality.8