Absent Cavum Septi Pellucidi

Abstract

The cavum septi pellucidi (CSP) is a small but important structure in the fetal brain. The CSP is a midline fluid-filled structure close to but distinct from the ventricular system. The cavum represents the actual space filled with cerebrospinal fluid (CSF) between the 2 thin septi pellucidi. The CSP is bordered laterally by the anterior horns of the lateral ventricles, superiorly by the corpus callosum, and inferiorly by the fornix. The CSP is typically fully formed at 17 weeks of gestation.1Loeser J.D. Alvord Jr., E.C. Agenesis of the corpus callosum.Brain. 1968; 91: 553-570Crossref PubMed Scopus (121) Google Scholar Throughout gestation, the CSP gradually closes, and after 37 weeks of gestation, it is usually no longer detectable ultrasonographically.2Falco P. Gabrielli S. Visentin A. Perolo A. Pilu G. Bovicelli L. Transabdominal sonography of the cavum septum pellucidum in normal fetuses in the second and third trimesters of pregnancy.Ultrasound Obstet Gynecol. 2000; 16: 549-553Crossref PubMed Scopus (55) Google Scholar Visualization of the CSP during prenatal ultrasound is essential for confirmation of normal brain anatomy.3Winter T.C. Kennedy A.M. Byrne J. Woodward P.J. The cavum septi pellucidi: why is it important?.J Ultrasound Med. 2010; 29: 427-444Crossref PubMed Scopus (60) Google Scholar Absence of the CSP is associated with several central nervous system (CNS) anomalies. Neurocognitive outcomes can vary in children born with an absent CSP and depend largely on associated findings. In the axial plane, the CSP is seen as an anechoic area of CSF (the cavum) medially that sits between 2 parallel echogenic lines (the 2 bordering septi pellucidi) laterally (Figures 1, 2, and 3). Care must be taken to avoid mistaking the columns of the fornix for the CSP (Figure 2, B).4Callen P.W. Callen A.L. Glenn O.A. Toi A. Columns of the fornix, not to be mistaken for the cavum septi pellucidi on prenatal sonography.J Ultrasound Med. 2008; 27: 25-31Crossref PubMed Scopus (32) Google Scholar The fornix is composed of 3 echogenic lines, whereas the CSP is composed of 2 echogenic lines. The fornix also does not contain CSF. In cases of an apparently absent CSP, a detailed neurosonogram that includes visualization of the coronal and median planes using 2-dimensional and 3-dimensional ultrasonography, and color Doppler should be performed (Figure 3). Fetal magnetic resonance imaging (MRI) should be obtained when available to confirm the diagnosis and to evaluate for other CNS abnormalities not apparent on ultrasound.Figure 2Axial sections demonstrating absence of CSPShow full captionA, The axial section (transventricular plane) shows the anterior horns communicating owing to the absent septae of the CSP. B, This axial section was obtained a few millimeters below the plane in which the CSP should be seen. The fornices can be differentiated from the CSP by the central third line present.SMFM. SMFM Anomalies Consult Series #3. Am J Obstet Gynecol 2020.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Transvaginally obtained 3-dimensional orthogonal planes and reconstructed axial planeShow full captionA, Coronal plane demonstrating absent septae. Note that the anterior horns of the lateral ventricles communicate with the cavum. B, Median sagittal plane demonstrating a normal-appearing corpus callosum. C and D, Axial planes demonstrating the boxlike shape of the ventricles, which communicate with the lateral ventricles.SMFM. SMFM Anomalies Consult Series #3. Am J Obstet Gynecol 2020.View Large Image Figure ViewerDownload Hi-res image Download (PPT) A, The axial section (transventricular plane) shows the anterior horns communicating owing to the absent septae of the CSP. B, This axial section was obtained a few millimeters below the plane in which the CSP should be seen. The fornices can be differentiated from the CSP by the central third line present. SMFM. SMFM Anomalies Consult Series #3. Am J Obstet Gynecol 2020. A, Coronal plane demonstrating absent septae. Note that the anterior horns of the lateral ventricles communicate with the cavum. B, Median sagittal plane demonstrating a normal-appearing corpus callosum. C and D, Axial planes demonstrating the boxlike shape of the ventricles, which communicate with the lateral ventricles. SMFM. SMFM Anomalies Consult Series #3. Am J Obstet Gynecol 2020. Embryologically, the development of the corpus callosum and the CSP is closely related.5Rakic P. Yakovlev P.I. Development of the corpus callosum and cavum septi in man.J Comp Neurol. 1968; 132: 45-72Crossref PubMed Scopus (448) Google Scholar When the CSP is not visualized, the next step should be a detailed neurosonogram to identify the corpus callosum and the pericallosal artery in the median or sagittal plane. There are 2 pericallosal arteries, one in the medial surface of each brain hemisphere. Coronal views are also helpful in identifying the hypoechoic corpus callosum below the interhemispheric fissure and above the lateral ventricles. The frontal horns are connected, resulting in a boxlike appearance. The thalami and the fornices are not fused. The lateral ventricles can be normal or have minimal dilation. Absent CSP is commonly associated with other CNS anomalies. Although an absent CSP can be an isolated finding,6Malinger G. Lev D. Oren M. Lerman-Sagie T. Non-visualization of the cavum septi pellucidi is not synonymous with agenesis of the corpus callosum.Ultrasound Obstet Gynecol. 2012; 40: 165-170Crossref PubMed Scopus (25) Google Scholar, 7Damaj L. Bruneau B. Ferry M. et al.Pediatric outcome of children with the prenatal diagnosis of isolated septal agenesis.Prenat Diagn. 2010; 30: 1143-1150Crossref PubMed Scopus (23) Google Scholar, 8Pilliod R.A. Pettersson D.R. Gibson T. et al.Diagnostic accuracy and clinical outcomes associated with prenatal diagnosis of fetal absent cavum septi pellucidi.Prenat Diagn. 2018; 38: 395-401Crossref PubMed Scopus (8) Google Scholar other authors have reported a high association with other anomalies.9Malinger G. Lev D. Kidron D. Heredia F. Hershkovitz R. Lerman-Sagie T. Differential diagnosis in fetuses with absent septum pellucidum.Ultrasound Obstet Gynecol. 2005; 25: 42-49Crossref PubMed Scopus (77) Google Scholar,10Barkovich A.J. Norman D. Absence of the septum pellucidum: a useful sign in the diagnosis of congenital brain malformations.AJR Am J Roentgenol. 1989; 152: 353-360Crossref PubMed Scopus (90) Google Scholar These specific findings depend largely on the etiology of the absent CSP. Some of these structural abnormalities may be identified by ultrasound, whereas others are difficult to visualize and may only be seen with prenatal or postnatal MRI. The differential diagnosis of an absent CSP includes several other CNS anomalies. Absent CSP is most commonly associated with holoprosencephaly (HPE), ventriculomegaly, septo-optic dysplasia (SOD), agenesis of the corpus callosum (ACC), and schizencephaly. Signs of alobar HPE on ultrasound include a large single fused ventricle, fused thalami, and absent midline brain structures. In semilobar and lobar HPEs, CNS findings are more subtle and include fused frontal lobes but distinct occipital lobes, absent interhemispheric fissure, and partial or complete ACC. Severe ventriculomegaly can also lead to nonvisualization of the CSP.10Barkovich A.J. Norman D. Absence of the septum pellucidum: a useful sign in the diagnosis of congenital brain malformations.AJR Am J Roentgenol. 1989; 152: 353-360Crossref PubMed Scopus (90) Google Scholar Severe ventriculomegaly may be caused by aqueductal stenosis in the setting of Chiari malformation type II or other factors. The increased pressure within the ventricles may cause fenestrations in the septi pellucidi and obliteration of the CSP. SOD is characterized by hypoplastic optic nerves, visual problems, and hypothalamic-pituitary dysfunction. Despite the increased sensitivity of prenatal MRI in the detection of fetal CNS anomalies, it does not readily detect optic tract hypoplasia. Postnatal brain MRI, along with ophthalmologic examination and endocrinologic studies, is used to make the clinical diagnosis of SOD.11Webb E.A. Dattani M.T. Septo-optic dysplasia.Eur J Hum Genet. 2010; 18: 393-397Crossref PubMed Scopus (140) Google Scholar In approximately two-thirds of cases of schizencephaly, the CSP may be absent.12Hosseinzadeh K. Luo J. Borhani A. Hill L. Non-visualisation of cavum septi pellucidi: implication in prenatal diagnosis?.Insights Imaging. 2013; 4: 357-367Crossref PubMed Google Scholar Schizencephaly represents a cortical defect that extends to the ventricles and may be difficult to diagnose ultrasonographically. Fetal MRI may improve detection rates of schizencephaly.13Lee W. Comstock C.H. Kazmierczak C. et al.Prenatal diagnostic challenges and pitfalls for schizencephaly.J Ultrasound Med. 2009; 28: 1379-1384Crossref PubMed Scopus (6) Google Scholar Some of the CNS anomalies associated with absent CSP are linked to genetic abnormalities. For example, HPE is associated with aneuploidy, and ACC is associated with many genetic syndromes.14Central nervous system: agenesis of the corpus callosum (ACC).in: Sanders R. Blackman L. Hogge W.A. Wulfsberg E.A. Speval P.J. Structural fetal abnormalities: the total picture. 2nd ed. CV Mosby Company, St Louis, MO2002: 17Google Scholar Diagnostic testing (amniocentesis or chorionic villus sampling) with chromosomal microarray analysis (CMA) should be offered when absent CSP is detected. It is reasonable to initially perform karyotype analysis or fluorescence in situ hybridization, with reflex to CMA if these test results are normal. If there are additional anomalies, consanguinity, or a family history of a specific condition, gene panel testing or exome sequencing is sometimes useful because CMA does not detect single-gene (Mendelian) disorders. If exome sequencing is pursued, appropriate pretest and posttest genetic counseling by a provider experienced in the complexities of genomic sequencing are recommended. After appropriate counseling, cell-free DNA screening is an option for patients who decline diagnostic evaluation, although it will not identify the underlying genetic cause in most cases unless a common aneuploidy is suspected. In most cases, an absent CSP should not alter the timing or mode of delivery. Exceptions include cases with severe ventriculomegaly and significantly increased head circumference, which may warrant consideration for cesarean delivery. In the presence of associated abnormalities that may require immediate neonatal intervention (eg, severe ventriculomegaly or trisomy 13 with planned full neonatal resuscitation), delivery should take place in a tertiary care center. In the absence of such findings, delivery in a community setting is reasonable, and decisions about the timing and mode of delivery should be guided by the usual indications. The prognosis of an absent CSP is largely dependent on the presence or absence of associated structural or genetic abnormalities. There is a paucity of data regarding the long-term neurodevelopmental prognosis of isolated absent CSP, and available data show variable outcomes. A study by Damaj et al7Damaj L. Bruneau B. Ferry M. et al.Pediatric outcome of children with the prenatal diagnosis of isolated septal agenesis.Prenat Diagn. 2010; 30: 1143-1150Crossref PubMed Scopus (23) Google Scholar showed good neurodevelopmental outcomes overall in 17 cases of isolated absent CSP. Of these 17 patients, 3 exhibited behavioral problems, and 2 had delayed language development. There were 3 cases of SOD diagnosed in the postnatal period. Another study8Pilliod R.A. Pettersson D.R. Gibson T. et al.Diagnostic accuracy and clinical outcomes associated with prenatal diagnosis of fetal absent cavum septi pellucidi.Prenat Diagn. 2018; 38: 395-401Crossref PubMed Scopus (8) Google Scholar identified 15 cases of isolated absent CSP. Clinical follow-up past the neonatal period was only available for 8 infants. In 6 infants with normal optic nerves and no hypothalamic-pituitary abnormalities, 3 had normal outcomes during follow-up. Furthermore, 1 patient had unilateral proptosis and astigmatism, 1 had increased tone in the upper and lower extremities, and 1 had mild gross motor delay. Two other patients for whom outcomes were available had hypoplastic optic nerves diagnosed postnatally. One infant had significant visual problems but no other developmental issues, and the other had hypoplastic optic nerves, panhypopituitarism, and social developmental delay. A recent study15Vawter-Lee M.M. Wasserman H. Thomas C.W. et al.Outcome of isolated absent septum pellucidum diagnosed by fetal magnetic resonance imaging (MRI) scan.J Child Neurol. 2018; 33: 693-699Crossref PubMed Scopus (9) Google Scholar included 8 patients diagnosed with isolated absent CSP on prenatal MRI. Among the patients, 2 were diagnosed with SOD postnatally, whereas the other 6 had normal ophthalmologic and endocrinologic evaluations and normal neurodevelopmental outcomes. The CSP is an important structure of the fetal brain, and its absence may have significant implications for fetal brain structure and neurodevelopmental outcomes. Documenting the presence of the CSP is of paramount importance on prenatal ultrasound. Another normal brain structure, the fornix, may be mistaken for the CSP in cases in which the CSP is congenitally absent. When the CSP is not seen on ultrasound, a prenatal MRI should be obtained if the technology and expert interpretation are available. MRI can be useful both in confirming or refuting the diagnosis and in identifying additional abnormalities not seen ultrasonographically. Diagnostic genetic testing should be offered because of known genetic abnormalities associated with various etiologies of absent CSP. The timing and mode of delivery typically are not altered by the diagnosis of absent CSP. If other serious abnormalities are present that require immediate treatment of the newborn, delivery should take place in a tertiary care setting. Neurodevelopmental outcomes in isolated absent CSP appear reassuring overall, although the data are sparse. The prognosis depends largely on the presence and type of associated anomalies.