ABSENCE OF THE CAVUM SEPTUM PELLUCIDUM

Since 2003 visualization of the cavum septum pellucidum (CSP) has been part of the standard 2nd trimester fetal anatomic survey1. The role of the anatomic survey is to detect the more common significant fetal congenital anomalies. Nervous, respiratory and cardiovascular malformations account for 60% of all malformations deaths2.

The cavum septum pellucidum can be imaged in the 2nd and 3rd trimester. Its presence provides reassurance of normal forebrain development. Non-visualization of the CSP has been associated with the forebrain abnormalities outlined in Table I.

Table I. Forebrain Abnormalities Associated with Congenital Absence of the Cavum Septum Pellucidum6,8,13

Normal Anatomy

The corpus callosum (Fig. 1) begins to develop at around 12 weeks’ gestation. The subsequent cavitation of the medial inferior commissural plate gives rise to the two septa pellucida (Fig. 2). The thin parallel septa pellucida separate the frontal horns of the lateral ventricles (Fig. 3). The space between the septa pellucida is filled with cerebrospinal fluid. In the past, the inferiorly positioned columns of the fornix have been mistaken for the CSP (Fig. 4)3.

Figure 1. Normal corpus callosum (arrow).
Figure 2. CSP 19 wks (arrow).
Figure 3. Normal coronal image of CSP (arrow).
Figure 4. Columns of the fornix (arrow).

The septum pellucidum is part of the limbic system and has connections to the hypothalamus, hippocampus, and amydala4,5. The CSP reaches its adult configuration by 17 weeks’ gestation5,6. The CSP can be documented in virtually 100% of cases between 18 and 37 weeks’ gestation. The detection rate declines to 79% between 38 and 41 weeks’ gestation. Hence, failure to detect the CSP prior to 18 weeks or after 37 weeks should be considered a normal finding7,8. By 6 months of age the CSP is obliterated in 85% of infants9,10. The eventual obliteration of a CSP in neonates is due to the rapid growth of the hippocampus and corpus callosum and the growing together of the cerebral hemispheres. As a result, the leaves of the septum pellucidum approximate and eventually fuse5.

The mean CSP width between 18 and 40 weeks’ gestation increases from 3.2 to 7.1 mm. In fetuses with trisomy 18, the CSP width is > 95th centile in 92% of cases (Fig. 5)11.

Figure 5. Enlarged CSP (arrow) associated with trisomy 18.
Figure 6. Absent CSP – fused anterior horns; coronal transvaginal image.

The absence of the CSP may be due to either a developmental anomaly or a secondary disruption.

Failure to visualize the CSP on the standard transaxial image between 18 and 37 weeks’ gestation should alert the sonologist to the possibility of agenesis of the corpus callosum. A detailed three-dimensional multiplanarneurosonographic examination should then be performed in order to more carefully evaluate the central neuraxis. The higher frequency of transvaginal probes provides greater resolution of fetal anatomy (Fig. 6).

Isolated Absence of the Septum Pellucium

The estimated incidence of an isolated absent CSP is 1/2000 neonates12. Approximately 20% of cases with an absent CSP are isolated12. Hence, absence of the CSP is not always diagnostic of a severe central nervous system abnormality13.

Sonographic Findings

With absence of the CSP, a coronal image reveals communicating squared off frontal horns and an absent cavum septum pellucidum (Fig. 6)14.

Prognosis

The long term outcome with isolated septal agenesis ranges from normal neurologic development to developmental delay and behavioral problems15.

Agenesis of the Corpus Callosum

Because of the embryologic linkage between the CSP and corpus callosum, abnormalities of the corpus callosum should first be considered when a CSP is not identified.

The rostral part of the corpus callosum (genu) forms first and then grows caudally to form the body and splenum16. Some studies suggest that the corpus callosum starts with formation of the anterior body and then progresses bi-directionally17. By 18-20 weeks’ gestation, the corpus callosum has assumed its final shape (Fig. 7).

Figure 7. 3D normal corpus callosum (arrow).

Partial absence of the anterior corpus callosum suggests a disruptive event; i.e. a vascular event or infection. An arrest of development is considered the etiology of an absent posterior corpus callosum17.

With partial absence of the anterior corpus callosum, an absence of the CSP may be detected. When there is absence of only the posterior corpus callosum, the indirect signs of ACC, such as absence of the CSP and colpocephaly will not occur. Hence, in fetal studies, the incidence of complete ACC is far higher than for partial ACC. In neonatal studies, with a more complete assessment of the central neuraxis, the incidence of the complete and partial ACC is equivalent18.

Since the gestational age dependent growth of the corpus callosum is known8, hypoplasia or thinning of the corpus callosum can be suggested, but not diagnosed with certainty. The estimated prevalence of ACC and hypoplasia of the corpus callosum is 1.4/10,000 and 0.4/10,000 livebirths, respectively19. Because of the low prevalence of disease, the 5th centile for callosal thickness would not be an appropriate threshold to diagnosis an abnormality17.

Absence of the corpus callosum may be either isolated or complex, i.e. associated with other anomalies.

Table II. Sonographic findings with Agenesis of the Corpus Callosum20

The sonographic findings associated with ACC are outlined in Table II. As previously mentioned, absence of the CSP is not specific for ACC. With ACC a lipoma or cyst (Fig. 8) may be present in the position of the CSP. On a transaxial image, there is dilatation of the occipital horns of the lateral ventricles (colpocephaly) (Fig. 9). Approximately 10% of cases of mild ventriculomegaly have ACC (Fig. 8)20,21,22. The increased separation of the lateral ventricles results in a prominent inter-hemispheric fissure.

Figure 8. ACC. Mild ventriculomegaly; cyst (arrow) at the level of the CSP.
Figure 9. Agenesis of the corpus callous. Colpocephaly (arrow).

The corpus callosum is best imaged mid-sagittally. The pericallosal artery can be used as a useful marker to identify the normal corpus callosum (Fig. 10).

Figure 10. Parasagittal image normal - corpus callosum and pericallosal artery (arrow).

There are associated brain abnormalities in approximately half of the cases with ACC. Subtle brain abnormalities, not detectable sonographically, include abnormal gyration patterns and heterotopia17.

Despite the numerous sonographic findings associated with ACC, the false positive diagnosis ranges up to 20%17. MRI is, therefore, helpful, not only to confirm the diagnosis, but also to evaluate the fetus for additional subtle associated brain abnormalities that may affect prognosis.

Chromosomal abnormalities are primarily associated with complex cases of ACC23. Approximately 15% of cases of ACC thought to be isolated have associated abnormalities17,24. Since the identification of complex cases of ACC with ultrasound is limited, fetal karyotyping in all cases of ACC would seem prudent.

Neonatal Outcome

The neurologic outcome after a prenatal diagnosis of isolated ACC ranges from normal to severe disability. The rate of neurodevelopmental delay with both partial and complete ACC is around 25%17,24,25.

While isolated ACC may be a benign finding, there are rarer conditions with absence of the CSP that should be considered: septo-optic dysplasia, Aicardi syndrome, and Acrocallosal syndrome. In view of the differential diagnosis and complexity of the syndromes involved, an accurate diagnosis of isolated absence of the CSP cannot be made with prenatal imaging.

Septo-optic Dysplasia (SOD)

Isolated absence of the CSP with downward pointing of the frontal horns (Fig. 11) is a sonographic finding associated with septo-optic dysplasia (SOD). Other findings with SOD include optic dysplasia and hypothalamic pituitary dysfunction. When a prenatal diagnosis of absent CSP is made, a fetal MRI may demonstrate specific associated features, i.e. unilateral or bilateral optic nerve hypoplasia. There is an associated variable degree of visual impairment. Low maternal serum estriol is present in 50-90% of cases of SOD due to fetal hypopituitarism. Unfortunately, SOD cannot be completely ruled out prenatally14,26,27. Neurologic abnormalities associated with SOD include epilepsy, mental delay, microopthlamia, anopthalmia and behavioral disorders15.

Figure 11. Septo-optic dysplasia. Transvaginal coronal image. Absence of the CSP with communicating frontal horns. There is downward pointing of the frontal horns (arrows).

SOD-plus is a syndrome with SOD and a spectrum of neurologic anomalies. Schizencephaly is one neurologic abnormality associated with SOD-plus28.

Aicardi Syndrome

Agenesis of the corpus callosum is part of the Aicardi syndrome. This is an X-linked dominant disorder with early embryonic demise in males. The surviving females have seizures and developmental delay.

The incidence of Aicardi syndrome in the United States is 1/105,00029. If only females are considered, ACC has an estimated incidence of 0.7/10,000. Hence, approximately 3.5% of isolated ACC in females will have Aicardi syndrome. The determination of a male karyotype is the only way to currently exclude this diagnosis in utero. Hence, patient counseling after a diagnosis of ACC in a female fetus must include this diagnosis as a consideration.

Acrocallosal Syndrome

This syndrome may be suspected if ACC is associated with postaxial polydactyly of the feet. Additional features of this autosomal recessive syndrome include multiple dysmorphic features – hypertelorism, frontal bossing, malformed ears – and subsequent motor and mental delay30.

Schizencephaly

Schizencephaly is a congenital brain abnormality characterized by clefts lined by gray matter that extends from the surface of the brain to the lateral ventricle. The lateral ventricle communicates directly with the sub-archnoid space (Fig. 12)31,32,33. The clefts in schizencephaly arise along the distribution of the middle cerebral artery.

Figure 12. Schizencephaly. Cleft (markers) extending from the surface of the brain to the lateral ventricles.

When schizencephaly is due to a disorder of migration, it occurs in the first two months of gestation. It may also occur later due to a vascular accident31.

Absence of the cavum septum pellucidum occurs in two-thirds of schizencephaly cases32,34.

Depending upon its size and location, schizencephaly may be difficult to distinguish from porencephaly – an intracerebral cavitation secondary to a destructive lesion33. The presence of gray matter along the cleft helps to distinguish schizencephaly from a porencephalic cyst33.

The degree of neurologic impairment with schizencephaly is dependent upon the amount of affected cerebrum and may include developmental delay, microcephaly, some degree of paralysis, and epilepsy32.

References

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