the cavum septi pellucidi · 2019. 7. 2. · jan byrne, md, paula j. woodward, md objective. the...

The Cavum Septi PellucidiWhy Is It Important?

Thomas C. Winter, MD, Anne M. Kennedy, MBBCh,Jan Byrne, MD, Paula J. Woodward, MD

Objective. The cavum septi pellucidi (CSP) is routinely imaged in the fetal brain during obstetric sonog-raphy; in fact, for well over a decade, assessment of the CSP has been considered part of the requiredelements of a standard examination of fetal morphology in guidelines developed by multiple specialtysocieties. Our objective is to present the 4 reasons why all practicing sonologists and sonographersshould be familiar with this anatomic structure. Methods. Prenatal sonograms and magnetic reso-nance imaging examinations are used to review the following topics: terminology, embryology, andanatomy of the CSP; pitfalls in its identification; and a wide variety of abnormalities (predominantlyrelating to nonvisualization) associated with the CSP. Results. Embryologic development of the CSP isintimately associated with the corpus callosum (CC); thus, correct identification of the CSP essentiallyexcludes complete agenesis of the CC. Absence of the CSP is associated with an extremely wide spec-trum of neuroanatomic malformations: these range from the lethal entities of hydranencephaly andalobar holoprosencephaly; to the potentially serious but nonlethal entities of schizencephaly, poren-cephaly, basilar encephaloceles, severe hydrocephalus, and the less severe prosencephalic cleavage dis-orders (including syntelencephaly); to the normal variant, the rare and somewhat controversial entityof isolated septal deficiency. The value of noting that the absent CSP allows diagnosis of very subtleand easily overlooked abnormalities such as septo-optic dysplasia is presented. Conclusions. Correctrecognition of the CSP provides welcome reassurance of proper development of the central forebrain.Key words: cavum septi pellucidi; corpus callosum; prenatal diagnosis; prosencephalon; sonography.

Received September 12, 2009, from the AbdominalImaging Section, Department of DiagnosticRadiology (T.C.W., A.M.K., P.J.W.), and Maternal-Fetal Medicine Section, Department of Obstetricsand Gynecology (J.B.), University of Utah MedicalCenter, Salt Lake City, Utah USA. Revision request-ed September 28, 2009. Revised manuscript accept-ed for publication December 3, 2009.

Address correspondence to Thomas C. Winter,MD, Department of Radiology, University of Utah,30 N 1900 E, Room 1A071, Salt Lake City, UT 84132-2140 USA.

AbbreviationsACC, agenesis of the corpus callosum; CC, corpus cal-losum; CNS, central nervous system; CSP, cavum septipellucidi; CV, cavum vergae; HPE, holoprosencephaly;MRI, magnetic resonance imaging; SOD, septo-opticdysplasia

he cavum septi pellucidi (CSP) is routinelyimaged on views of the fetal brain obtained dur-ing obstetric sonography. Assessment of the CSPis considered part of the minimum elements of

a standard examination of fetal anatomy in guidelinesdeveloped by the American Institute of Ultrasound inMedicine in collaboration with the American College ofRadiology and the American College of Obstetricians andGynecologists,1,2 as well as by virtually all other profes-sional guidelines and reviews.3–8

Nonvisualization of the CSP is an important observa-tion with important consequences for the fetus and thepregnancy. Absence of the CSP has been associated witha wide variety of outcomes, ranging from devastating toincidental. Associations include the spectrum of holo-prosencephaly (HPE), from alobar to lobar, and the morerecently described entity of syntelencephaly; septo-opticdysplasia (SOD); callosal dysgenesis and hypogenesis;chronic severe hydrocephalus, typically from aqueductal

© 2010 by the American Institute of Ultrasound in Medicine • J Ultrasound Med 2010; 29:427–444 • 0278-4297/10/$3.50

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stenosis or the Chiari II malformation; schizen-cephaly; porencephaly/hydranencephaly; basilarencephaloceles; and isolated septal deficiency.9–11

This manuscript will review prenatal sonogra-phy and magnetic resonance imaging (MRI) ofthe CSP, including anatomy, embryology, andscan techniques. The differential diagnosis for anabsent CSP and consequences for managementare discussed.

Anatomy and Embryology

Anatomy and scan techniques are well describedin standard texts12,13; a superb, more detaileddescription of the anatomy of the CSP and cor-pus callosum (CC) may be found in a 2008 articleby Callen et al.9

The CSP is conceptually regarded as a part ofthe longitudinal cerebral fissure, which becomeswalled off by the union of the hemispheres form-ing the CC above and the fornix below.9,14

More specifically, at about 12 weeks’ gestation-al age, the CC starts to develop from the laminaterminalis as a bundle of fibers that connectsthe two hemispheres. This is associated with thedevelopment of the septa pellucida, two pairedclear membranes. The space between the septais one cavity but has two different names; anteri-or to the foramina of Monro, it is called the CSP,whereas posterior to this structure, it is called thecavum vergae (CV).9 Other authors use differentterminology but the equivalent position anatom-ically: a vertical plane defined by the columns ofthe fornix (from Latin, a vaultlike or arched struc-ture) as the division between the CSP and theCV.15,16 Of note, although correctly the entirespace is the “CSP et vergae,”9 in common usage(and unless specified otherwise throughout thisarticle), the entire cavity is often just called theCSP. In most individuals, the cavum (literally, ahollow space, hole, or cavity) is closed early inchildhood, and the two septa are fused. Thefused membranes, now using the Latin singular,are properly referred to as the septum pellu-cidum.17 This closure of the CSP et vergae beginsat approximately 6 months’ gestational age andprogresses from back to front. By term, closurehas occurred posteriorly in 97%, so that there isgenerally only a true CSP at birth; by 3 to 6months of age, the CSP is closed in 85% of

infants,18 although in a minority this cavityremains open until adulthood.19

Although there is no direct evidence to suggestthat the CSP cannot develop independently fromthe CC, the CC is closely related anatomically andembryologically to the CSP; most authors statethat there cannot be a CSP without a CC.13 Boththe CC and the CSP develop from the commis-sural plate.9 Conversely, it is possible to have anormal CC without a normal CSP, eg, in isolatedseptal deficiency or SOD.

The CC forms late in cerebral ontogenesis,between 12 and 18 weeks13 or alternatively 8 and20 weeks19 (depending on the citation). Mostauthorities state that the CC forms from front toback (ventrally to dorsally), beginning with therostrum, then the genu, body, and splenium,13,17

although fetal MRI and other data suggest thatthe genu and anterior body form first, with devel-opment then proceeding both anteriorly to therostrum and posteriorly to the splenium.19,20

Sonography

The CSP is routinely imaged on the 3 obligatoryviews of the fetal head obtained during obstetricsonography. Specifically, in addition to theimages of the ventricles and the posterior fossa,an axial view at the level of the paired thalamiyields both the biparietal diameter and theCSP.13,21 Under normal conditions, the CSPshould be easily seen beyond approximately 18 to20 weeks.13,17,22,23 A variety of sonographic andMR images of the normal CSP, both prenatal andpostnatal, are provided (Figures 1–3).

Proper attention to technique is crucial in notmistakenly calling the CSP present when it istruly absent.24 The CSP must range from themedial wall of the frontal horn of one lateral ven-tricle to the medial wall of the frontal horn of thecontralateral lateral ventricle; if it does not, oneruns the risk of ignoring true absence of the CSPand missing associated neurologic abnormali-ties.25 Pilu et al24 have described an artifact mim-icking the presence of the CSP in standard axialsecond-trimester sonographic images of thebrain; thus, if the CSP is not seen with certaintyon standard axial images, obtain a series of coro-nal images, and also attempt to identify the CCdirectly with a midsagittal view.9

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The Cavum Septi Pellucidi: Why Is It Important?


Part of the problem in mistakenly calling a CSPpresent when it is indeed absent relates to confus-ing normal anatomy, the paired nerve columns of

the fornix, with the CSP (Figure 4). Because theembryologic development of the fornix is notclosely correlated with that of the CC, demon-stration of the fornix will not exclude abnor-malities of the CC and other central forebrainmalformations.9 Recall that the CSP can beregarded as part of the longitudinal cerebral fis-sure, which is walled off by the CC above and thefornix below during embryologic development.

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Figure 1. Normal CSP in utero by second-trimester sonography.The CSP appears as a fluid-filled box between the paired septa(arrows), which separate the CSP from the frontal horns of thelateral ventricles. A, Axial. Note the absence of the centralechogenic line in the center of the CSP, a finding that helps pre-vent misinterpretation of the fornix as the CSP (see Figure 4).Anterior is to the reader’s left. B, Coronal. The loss of detail onthe viewer’s right is due to near-field reverberation.

A

B

Figure 2. Normal CSP postnatally by MRI. Axial (A) and coronal(B) images of the normal CSP in a term neonate show the nor-mal appearance of the CSP (arrows).

A

B


Thus, paired adjacent hypoechoic structures inthe forebrain in a plane of section just caudal tothe axial plane that delineates the CSP representthe fornix; if the CSP is absent, the fornix may bemisinterpreted as the CSP.9 The normal CSPshould appear as a white line (lateral margin ofthe CSP), dark box (fluid within the CSP), andwhite line (lateral margin of the opposite side ofthe CSP), whereas the fornix will appear as awhite line (lateral margin of one of the fornices),dark area (substance of one of the fornices),white line (interface between the paired for-nices), dark area (substance of the other fornix),and white line (lateral margin of the otherfornix).

A squared appearance to the frontal horns oncoronal views should suggest the possibility ofabsence of the CSP.26

What is the normal size of the CSP? Jou et al27

studied more than 600 consecutive fetusesbetween 19 and 42 weeks of age and found that at19 to 20 weeks, the mean width was 3.4 mm, and2 SD on either side ranged from 2.08 to 4.72 mm.A smaller study also noted a difference in the sizeof the CSP between the second and thirdtrimesters, with the mean width in the secondtrimester of 3.1 ± 1 SD of 1.5 mm.22

Magnetic Resonance Imaging

Techniques for fetal MRI have been welldescribed elsewhere.28 Note that fetal MRI isgenerally performed at a later gestational agethan routine fetal survey sonography due toboth technical reasons (fetal movement andsize) and the fact that some brain abnormali-ties may not be detectable until later in preg-nancy. Fetal MRI adds useful information inmany patients with sonographically detectedneurologic abnormalities. For example, in age-nesis of the corpus callosum (ACC), prenatalMRI finds other abnormalities that were missedon sonography in more than half of cases.29

Many of these, such as gray matter heterotopia,are too subtle to be readily detected by sonogra-phy. In addition to its intrinsic value in the fetalbrain, MRI often adds particular value inpatients in whom sonography is difficult, eg,maternal obesity and oligohydramnios.

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Figure 3. Normal variant CSP et vergae. The rectangular ane-choic structure directly underneath the paired arrows representsthe space between the two septa pellucida; anterior to theforamina of Monro, this cavity is denoted as the CSP, whereasposterior to the foramina of Monro, it is called the CV. This is asecond-trimester axial sonogram, with anterior to the reader’sleft.

Figure 4. Potential pitfall: fornix mistakenly identified as theCSP. The paired nerve columns of the fornix are located just infe-rior to the CSP. The hyperechoic lines (arrows) represent reflec-tions from the medial walls of the lateral ventricles, whereas thecentral echogenic line likely represents the interface between thecolumns of the fornix. This appearance has been reported to bemistaken for the CSP in a fetus with ACC.9 This is a second-trimester axial sonogram, with anterior to the reader’s left.

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Pathology

Absence of the CSP occurs as part of a large vari-ety of cerebral anomalies. In some instances,complex malformations are readily identifiedwith prenatal sonography, such as the spectrumof HPE and severe ventriculomegaly. Otheranomalies, particularly ACC, may be more subtle.Many of these associations are discussed below:

Agenesis of the Corpus CallosumAgenesis of the corpus callosum (Figures 5 and 6)is part of the spectrum of CC abnormalities,including hypogenesis and dysgenesis. It is oneof the most common central nervous system(CNS) anomalies (0.5–70 per 10,000 live birthsand 4% of CNS malformations30). Manifestationsare protean, from asymptomatic individualsto associated abnormalities, including hydro-

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Figure 5. Classic complete ACC. A, Axial third-trimester sonogram, with anterior to the reader’s left, shows colpocephaly (asterisk). B, Axialin utero third-trimester MRI shows parallel lateral ventricles. C, Coronal MRI shows a “Texas longhorn” configuration to the lateral ventri-cles, with absence of the CSP. D, Sagittal MRI shows complete absence of the CC. Note nonvisualization of the CSP on all images.

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C

B

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cephalus, lissencephaly, pachygyria, and micro-cephaly. More than 80 associated chromosomal(including trisomy 18 and 13), genetic, and spo-radic syndromes have been described.31 TheDandy-Walker malformation is one of the mostcommon associations11; callosal hypogenesis ispresent in up to one-third of patients with theDandy-Walker malformation (Figure 7).11

Because the CC largely forms from anterior toposterior, hypogenesis of the CC implies that thesplenium is always abnormal. Prenatal imagingmay show the classic finding of colpocephaly3

(focal dilatation of the trigones and occipitalhorns of the lateral ventricles) with the so-calledteardrop-shaped ventricles.10 The fibers thatshould have crossed to the opposite hemisphereturn at the interhemispheric fissure and run par-allel to it, forming the bundles of Probst. In turnthe Probst bundles displace the frontal horns ofthe lateral ventricles, giving them a crescenticshape, producing the steer horn or Viking helmetsign in the coronal plane.11 Other potential sono-graphic findings include a high-riding third ven-tricle between widely separated, parallel lateralventricles; several subtypes of interhemisphericcysts, not all of which communicate with theventricles; lipoma in the expected location of the

CC; vertical orientation of the radiating gyri(often seen best with a sagittal endovaginalapproach in the vertex fetus); and an abnormalcourse or absence of the pericallosal artery.12,31

Despite all of these findings, diagnosis of isolatedACC may be challenging, even for expert sonolo-gists, before 22 weeks.12,32 In particular, if the clas-sic colpocephaly is not appreciated, recognitionof the absence of the CSP prompts the sonologistto suggest the diagnosis of ACC.

Of note, infection, hemorrhage, and other inju-rious processes may lead to destruction of por-tions of the CC after normal initial formation. Inthis situation, the posterior portion of the callo-sum may be absent, but the CSP may still be pre-sent, so visualization of the CSP does not alwaysimply a completely normal CC.

Aicardi SyndromeThe initial clinical description was a triad ofinfantile spasms, ACC, and ocular abnormalities.In a female fetus, the combination of ACC withposterior fossa malformation (posterior fossacysts and cerebellar hypoplasia) and cortical dys-plasia suggests Aicardi syndrome, especially ifthere are eye abnormalities (eg, microphtlamiaand coloboma; Figure 8). Aicardi syndrome is an

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Figure 7. Agenesis of the CC associated with the Dandy Walkermalformation. A, Suboccipital bregmatic second-trimester sono-gram, with anterior to the reader’s left, shows a large cyst repre-senting the expanded fourth ventricle (C) (continued).

A

Figure 6. Pitfall: the high-riding third ventricle (asterisk) in thisfetus with ACC should not be confused for the CSP (which isabsent). Note also the colpocephaly (C, teardrop shape to theoccipital horns of the lateral ventricle). This is a second-trimesteraxial sonogram, with anterior to the reader’s left.


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Figure 7. (continued) B, Slightly oblique axial sonogram at thelevel of the lateral ventricles shows markedly dilated ventricleswith colpocephaly (F indicates frontal horn; and O, occipitalhorn) as well as the superior aspect of the expanded fourth ven-tricle (DW). C, Another suboccipital bregmatic sonogram alsoshows the relative sparing of the mildly dilated frontal horns ofthe lateral ventricles of colpocephaly as well as the expandedfourth ventricle (arrow). D, Coronal in utero third-trimester MRIshows a Texas longhorn configuration to the lateral ventricles,with absence of the CSP. E, Axial in utero MRI shows parallel lat-eral ventricles (left) and a large fourth ventricle in the posteriorfossa (right). F, Sagittal MRI shows complete absence of the CCand a large fourth ventricle in the posterior fossa. Note nonvi-sualization of the CSP on all images.

B

C F

E

D


X-linked dominant disorder seen in females withlethal consequences for male fetuses and is rarelyseen in 47,XXY karyotypes.11,31 The finding of reti-nal lacunae on postnatal ophthalmologic exami-nation confirms the diagnosis.

HoloprosencephalyHoloprosencephaly is a severe malformation ofthe brain characterized by abnormal cleavage of the prosencephalon in the fifth gestational week.

Most cases are sporadic, but chromosomal,genetic, and teratogenic causes have been dis-cussed.31 This entity has classically been dividedinto 3 subtypes by DeMeyer et al: alobar, semilo-bar, and lobar. To quote from the University ofCalifornia San Francisco group: “Alobar HPE, themost severe of the three types, generally appearsas a pancake-like mass of cerebral tissue and acrescentic monoventricle. Semilobar HPE ischaracterized by noncleaved anterior brain, with

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C D

Figure 8. Aicardi syndrome. A, Suboccipital bregmatic second-trimester sonogram, with anterior to the reader’s left, shows absenceof the CSP with interdigitating gyri in the anterior brain but a normal appearance to the cerebellum and posterior fossa. B, Axial sono-gram shows a posterior interhemispheric cyst (asterisk). C, In utero third-trimester axial MRI shows pachygyria and polymicrogyria. D, Sagittal MRI delineates a coloboma (arrow). A coloboma is a defect in which part of the eye, in this case the optic nerve, does notform correctly. The presence of a coloboma increases the likelihood of a syndromic diagnosis.33

BA


the posterior falx and posterior interhemispher-ic fissure (IHF) present. Lobar HPE is also char-acterized by anterior brain noncleavage thatexists to a lesser degree than that of semilobarHPE, a fully formed third ventricle, and somedevelopment of frontal horns of the lateral ven-tricles.”34 The alobar variety has been furthersubdivided by sonologists into 3 types basedon the residual cerebral tissue that appears in these forms: “pancake,” “cup,” and “ball.”13

As Barkovich11 states, though, the HPEs are a het-erogeneous group of forebrain malformations,with no clear distinction between the differentcategories having been firmly established; otherclassification systems have also been suggested.

Sonographic findings in HPE depend on theseverity of the forebrain cleavage malformation.In the alobar type (the easiest to recognize;absence of the CSP is overshadowed by the otherstriking sonographic findings; Figure 9), the falxand the interhemispheric fissure are totallyabsent; the thalami are fused; there is a singlemonoventricle, often described with a “horse-shoe” configuration; and the third ventricle, neu-rohypophysis, olfactory bulbs and tracts, CSP,CC, and interhemispheric fissure31 are absent. Insemilobar HPE (Figure 10), the monoventricle isstill present, but there is some separation of thecerebral hemispheres posteriorly. The thalamusmay be partially or fully fused but again withabsence of the third ventricle. A characteristicdorsal sac is often associated with the alobar andsemilobar forms. These first 2 types of HPE aregenerally easily recognized, but the correct find-ings in lobar HPE may be difficult to observe;again, absence of the CSP is particularly impor-tant in recognizing the subtle variants of lobarHPE. With lobar HPE (Figure 11), the brain isalmost completely divided into two hemi-spheres, with the exception being a variabledegree of fusion at the level of the cingulate gyrusand frontal horns of the lateral ventricles.13 Otherfindings helpful in lobar HPE are central fusionof the frontal horns with a flat, squared roof andcommunication with the upper portion of thethird ventricle on coronal imaging and fused for-nices35 appearing as a linear structure runningwithin the third ventricle from the anterior toposterior commissure.12,13,31 Some patients withlobar HPE likely fall into the spectrum of SOD.11

All types of HPE are often associated with micro-cephaly and less frequently with macrocephalydue to aqueductal stenosis leading to hydro-cephalus.12,13 A wide variety of midline facialabnormalities are often associated with HPE:hypotelorism or cyclopia, median cleft lip andpalate, a flat nose with a single naris (cebo-cephaly), and a proboscis superior to the level ofthe eyes (ethmocephaly).31

In 1993, Barkovich11 described a lesser knownfourth subtype of HPE, related to semilobarHPE, known as the midline interhemisphericfusion variant or syntelencephaly (Figure 12).Syntelencephaly consists of an abnormal mid-line connection of the cerebral hemispheresin the posterior frontal and parietal regions,with interhemispheric separation of the basalforebrain, anterior frontal lobes, and occipitalregions34,36; prenatal MRI of this entity has beenreported.37

Septo-optic DysplasiaSepto-optic dysplasia (also known as De Morsiersyndrome; Figure 13) is a rare congenital dis-order characterized by absence of the CSP,hypoplasia of the optic nerves and chiasm lead-ing to alterations in visual acuity, various types ofhypothalamic-pituitary dysfunction (includingalterations in growth hormone, antidiuretic hor-mone, thyroid-stimulating hormone, luteinizing

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Figure 9. Alobar HPE. Axial oblique (suboccipital bregmatic) sec-ond-trimester sonogram, with anterior to the reader’s left,denotes the classic crescenteric monoventricle, fused thalami(asterisk), and complete absence of normal midline structuressuch as the CSP, falx, and interhemispheric fissure.


hormone, and follicle-stimulating hormone lev-els) leading to growth delay, and associationswith developmental delay/intellectual impair-ment.23,24,38 It has been reported in associationwith valproic acid embryopathy.39 Septo-opticdysplasia can be distinguished from HPE by theabsence of fused thalami; typical lack of pro-nounced ventriculomegaly (although dilatedventricles may be present occasionally in SOD);and a normal appearance to the CC, columns ofthe fornix, anterior cerebral arteries, and falx

cerebri.23 An excellent discussion of SOD, includ-ing the diagnostic utility of low levels of gravidmaternal estriol, is provided by Lepinard et al23;potential associations of SOD with cleft lip andpalate, as well as cortical dysplasia, are discussed.Note that cortical dysplasias and some forebrainmalformations may not be detected by sonogra-phy or MRI before 30 to 32 weeks. As the resolu-tion of 2- and 3-dimensional sonography40 andMRI continues to improve, an effort may bemade to evaluate the optic chiasm and nerves for

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B D

Figure 10. Semilobar HPE. A, Axial second-trimester sonogram, with anterior to the reader’s left, shows absence of the CSP. Note howotherwise normal this image appears. B, Coronal sonogram shows a fused choroid plexus (arrows) across the midline. C and D, Axialsonogram (C) and third-trimester MRI (D) denote a fused frontal lobe cortex across the midline (asterisks) as well as absence of the CSP.

CA


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C D

Figure 11. Lobar HPE. A, Axial second-trimester sonogram,with anterior to the reader’s left, shows a round head, absenceof the CSP, and venticulomegaly. B, Coronal sonogram shows aclassic fused fornix (arrow), a frequent and reportedly specificsonographic finding for lobar HPE.35 C, Coronal postnatal(neonatal) sonogram of the head again denotes a classic fusedfornix (arrow). D, Axial postnatal MRI better delineates findingsfrom A. E, Coronal postnatal MRI replicates findings from B andC (arrow indicates fused fornix).

BA

E


additional information in cases of possible SOD.Counseling is difficult because SOD has such awide range of clinical presentations; it is impossi-ble to determine disease severity prenatally,23,38

and the diagnosis must be confirmed clinicallyafter birth. Recognition of absence of the CSP isessential to suggesting this diagnosis prenatally.

SchizencephalyThe cleft of schizencephaly (Figure 14) is ofuncertain etiology; in the past, it has been pro-posed that schizencephaly is part of a spectrumof encephaloclastic disorders due to vascularinfarction,41 although more recent work suggestsa neuronal migrational anomaly as perhaps a

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Figure 12. Syntelencephaly. A, Axial sonogram, with anterior to thereader’s left, of a 16-week fetus with the midline interhemisphericfusion variant of HPE shows absence of the CSP with a poorlydefined fluid collection in the midline (monoventricle) but with inter-hemispheric separation of the frontal lobes; note the anterior falx(arrow), which excludes classic HPE. B, Fetal autopsy coronal MRIshows abnormal midline connection (gyral contiguity) of the cere-bral hemispheres in the posterior frontal and parietal regions (arrow-heads). Also note paired, nonfused thalami (asterisks).

A

B

Figure 13. Septo-optic dysplasia. A, Axial sonogram, withanterior to the reader’s left, at 29 weeks denotes absence of thenormal box of the CSP between the frontal horns of the lateralventricles. B, Postnatal axial MRI again showing absence of theCSP. The diagnosis was confirmed clinically by ophthalmologicexamination.

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more likely etiology.42 Two types have beendescribed, both of which communicate with theventricles, ie, extend from the pia to ependyma.In the open-lipped form, the edges of the cleftare splayed apart, whereas in the close-lippedform, the edges are apposed. Associationsinclude enlarged ventricles, ACC, polymicrogyr-

ia, heterotopia, and absence of the CSP12,31;absence of the CSP is noted in 70% of schizen-cephaly cases, especially when bilateral.30

Schizencephaly can be difficult to diagnose withsonography in the second trimester, so nonvisu-alization of the CSP may be a useful clue.43 Otherterms that have been used for schizencephalyinclude “true porencephaly”13 and “ageneticporencephaly.”11

PorencephalyAlso known as pseudoporencephaly or encepha -loclastic porencephaly,12 this term is often usedas collective nomenclature for a variety of largecortical defects that may communicate with theventricles. Unlike schizencephaly, which is linedwith gray matter, the lining of the porencephaliccavity often contains white matter.13 The cavity isalmost never midline.

HydranencephalySonographic findings include replacement ofmost of the cerebral hemispheres with fluid withsparing of the brain stem and rhombencephalicstructures.12 Proposed etiologies include over-whelming antenatal infections and occlusion ofthe internal carotid arteries. Obviously, nonvisu-alization of the CSP is an expected finding, andrecognition of absence of the CSP is not crucialto making the diagnosis of this entity (Figure 15).

Chronic Severe HydrocephalusEtiologies of severe hydrocephalus associatedwith nonvisualization of the CSP include aque-ductal stenosis and the Chiari II malformation.26

Severe hydrocephalus may be difficult to distin-guish from hydranencephaly and alobar HPE.The presence of some cortical tissue (cup, ball, orpancake form) should be seen with alobar HPE; avery thin rind of cortex indicates extreme hydro-cephalus rather than hydranencephaly. Magneticresonance imaging is helpful to confirm the pres-ence of a cortical mantle. From a practical per-spective, hydranencephaly and alobar HPE havea similar dismal prognosis,13,31 the differentiationbeing of concern primarily in prediction ofrecurrence risk. Severe hydrocephalus of anytype with fenestration of the CSP is suggested asone of the more common causes of CSP nonvi-sualization on prenatal sonograms (Figure 16).

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Figure 14. Schizencephaly. A, Axial second-trimester sonogram,with anterior to the reader’s left, denotes absence of the CSP(arrow; again, note nonvisualization of the normal box betweenthe frontal horns of the lateral ventricles). An abnormal cleft inthe cortex (S) is seen rostral to the occipital horn (V). B, In uterothird-trimester MRI confirms the extent of defect from the pia toependyma (asterisk) and shows the gray matter lining.

A

B


Basilar EncephalocelesIn an article by Barkovich and Norman26 onabsence of the septum pellucidum, 2 of 3patients with basilar encephaloceles (Figure 17)also had ACC and absence of the CSP.

Isolated Septal DeficiencySeveral cases of isolated absence of the CSP havebeen reported.23,24 However, counseling is diffi-cult because apparently isolated absence of theCSP may be associated with cytoarchitecturaldisturbances of cortical layers not currentlydemonstrable by MRI.

Enlarged CSPAfter birth, an enlarged CSP (>1 cm) and persis-tence of a CSP beyond infancy have beendescribed as “true subtle markers of cerebral dys-genesis,”44 possibly associated with neuropsychi-atric disturbances27 (particularly schizophrenia16).It is not known with certainty what percentage offetuses with a wide CSP (Figure 18) will continueto have a wide CSP after delivery, but the largestseries we located described persistence of atransvaginally diagnosed enlarged CSP in thesecond trimester into the third trimester in 7 of 8fetuses.15 This series noted than an enlarged CSP

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Figure 15. Hydranencephaly. Note the characteristic appear-ance of the thalami and brain stem protruding within a cysticcavity without any frontal cortex present (the latter allowing dif-ferentiation from HPE and extreme hydrocephalus); as expected,there is absence of the CSP. As is often the case in hydranen-cephaly, the falx is present. A, Axial second-trimester sonogram,with anterior to the reader’s left, shows the intact falx, completelack of anterior cerebral tissue, and abnormal posterior tissue. B and C, Coronal third-trimester MRIs confirm the intact falx,lack of cerebral rind, and absent CSP and show the characteris-tic appearance of hydranencephaly.

A

B C


may be associated with hydrocephalus, chromo-somal translocation, and growth restriction butconcluded that when an enlarged CSP is an iso-lated finding, termination of pregnancy is notjustified, although the fetal karyotype should beobtained until more is known about the impor-tance of this entity.15 The differential diagnosisfor an enlarged CSP has been reported to includethe so-called vein of Galen aneurysm (althoughwith knowledge of neuroanatomy and access toDoppler technology, this possibility should notbe seriously entertained), arachnoid cyst, anddilated third ventricle16; the latter can be distin-guished by its location between the thalami,whereas the CSP is above the thalami andanterior to the third ventricle.15 The true clini-cal importance of a wide CSP prenatally is thusunknown, but it has been stated that this findingshould be followed by a detailed search for asso-ciated anomalies,15,16 and postnatal imaging anddevelopmental evaluation may be indicated.27

Conclusions

The CSP is an important marker for normal fetalCNS development. Although not as crucial asassessment of the lateral ventricular atrium and

cisterna magna,3 never assume that nonvisual-ization of the CSP is “technical”; an absent CSPmay be a marker of serious brain malforma-tion.10 In their oft-quoted postnatal MRI study,Barkovich and Norman26 concluded thatabsence of the CSP was never a normal finding.More experience has been obtained with prena-tal imaging since then, confirming that absenceof the CSP is rarely an isolated finding.

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Figure 16. Fenestrated CSP. Coronal second-trimester sono-gram shows absence of the normal CSP. This fetus has dilatedthird (3) and lateral (L) ventricles; other images showed a normalfourth ventricle. The obstructive hydrocephalus resulting fromaqueductal stenosis has torn the CSP so that only a remnant(arrow) is visualized.

A

Figure 17. Encephalocele. A, Suboccipital bregmatic sonogram,with anterior to the reader’s left, at 26 weeks shows encephalo-cele (asterisk) but no CSP. The faint hypoechoic structure seenanteriorly in the midline (arrow) represents the fornix, a normalstructure caudal to the CSP that is commonly mistaken for theCSP. The normal CSP must be a boxlike fluid-filled structure thatis bordered on either side by the medial walls of the frontal hornsof the lateral ventricles. B, Axial follow-up sonogram, with ante-rior to the reader’s left, at 32 weeks shows colpocephaly andabsence of the CSP; note how easy it is to miss absence of theCSP unless one is specifically looking for it.

B


Conversely, presence of the CSP virtually ensuresnormal development of the central forebrain,thereby excluding many complex malformations.3

In the most recent American Institute ofUltrasound in Medicine guideline,2 6 intracranialstructures represent the minimum elements ofa standard examination of fetal neuroanatomy:cerebellum, choroid plexus, cisterna magna, lat-

eral cerebral ventricles, midline falx, and CSP. In their seminal 1989 article “Detection of FetalCentral Nervous System Anomalies: A PracticalLevel of Effort for a Routine Sonogram,” Filly etal3 state that “identification of this easily demon-strated structure (the CSP) provides an addedmeasure of certainty that the fetal CNS has devel-oped normally.”

Equally as important as proper identification ofa normal CSP is not mistakenly calling otherstructures the CSP in the setting of abnormalmidline development. In other words, “don’tmake it up!” A classic pitfall already discussed isincorrectly attributing the paired columns of thefornix as the CSP; remember that the CSP islocated superior to the fornix and lacks the cen-tral linear echo seen in the fornix (Figure 4).Another potential error is simply noting fluidbetween the lateral margins of the frontal hornsand calling that a normal CSP. The CSP mustrange from the medial wall of the frontal horn ofone lateral ventricle to the medial wall of thefrontal horn of the contralateral lateral ventricle;note that in SOD (Figure 13), the normal “box”between the medial wall of the frontal horns isnot appreciated, a subtle abnormality that caneasily be mistaken as a normal CSP. In the exam-ple of schizencephaly (Figure 14) again note theabsence of the normal box between the medialwall of the frontal horns. Also, take care not toconfuse the high-riding third ventricle or promi-nent interhemispheric fissure for the CSP (Figure6); as mentioned before, the CSP is located ante-riorly and should be directly between the frontalhorns of the lateral ventricles. As a final potentialpitfall, remember that the CSP et vergae is nor-mal. Many sonologists struggle with a “big CSP”and mistakenly call it some type of midline cyst,when in fact it is just a long and normal CSP etvergae (Figure 3).

There are 4 main reasons why awarenessregarding the CSP is important. First, it isrequired by guidelines promulgated by multiplesocieties. Second, it is a marker for ACC, one ofthe most common CNS anomalies. AlthoughACC can be diagnosed after 18 to 20 weeks,especially in expert hands,13 it can be a difficultdiagnosis. Failure to visualize the CSP andcolpocephaly are crucial clues in suggesting ACC.Third, nonvisualization of the CSP is often one of

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A

Figure 18. Enlarged CSP (arrows) as an isolated finding in afetus who apparently had no abnormalities at both birth andshort-term follow-up. A, Axial second-trimester sonogram, withanterior to the reader’s left. B, Coronal sonogram. Both imagesshow a CSP that measured 8.7 mm.

B


the only clues to the diagnosis of certain entities,classically SOD. Fourth, knowledge of the CSPprovides an impetus to review and study manyother more obvious entities affecting the centralforebrain (eg, HPE, porencephaly, hydranen-cephaly, and severe hydrocephalus).

In summary, we have presented informationregarding the anatomy and embryology of theCSP; scan techniques for prenatal sonographyand MRI of this structure; prenatal examples of awide variety of entities, both common anduncommon, associated with absence of theCSP; differential diagnosis of various entitiesassociated with an absent CSP; and the poten-tial clinical importance of many of these entities.Visualization of a normal CSP is a strong indica-tor of proper development of the central fore-brain.

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the cavum septi pellucidi · 2019. 7. 2. · jan byrne, md, paula j. woodward, md objective. the...

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