Effects of failed commissuration on the septum pellucidum and fornix: implications for fetal imaging
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- Griffiths, P.D., Batty, R., Connolly, D.A.J. et al. Neuroradiology (2009) 51: 347. doi:10.1007/s00234-009-0507-x
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In the previous article, we considered the normal appearances of the midline stuctures of the brain as they appear on high-resolution magnetic resonance imaging. In this article, we discuss the effects of failed commissuration on the midline structures. We highlight some of the misconceptions of this process that may lead to misdiagnosis of agenesis of the corpus callosum in utero.
KeywordsMagnetic resonance imagingCorpus callosumSeptum pelucidumFornixFailed commissuration
In our previous paper, we reviewed the normal development and anatomy of the corpus callosum, septum pellucidum, and fornix along with some of the commoner anatomical variants as shown on MR imaging. In this paper, we build on those topics by discussing failed commissuration. One of the most clinically relevant of those abnormalities is agenesis of corpus callosum (ACC) as it is one of the most commonly detected brain abnormalities in fetal life and is associated with a high risk of developmental/neurological sequelae . The risk is particularly high when other brain abnormalities are present but ACC is considered to indicate a poor prognosis by many groups even when it is an isolated finding [1, 2].
Recent work has compared the results of fetal ultrasonography and in utero MR (iuMR) imaging and has shown that ACC (and hypoplasia) is diagnosed with greater accuracy when iuMR is included in the diagnostic process [3–5]. This appears to be true for both second and third trimester imaging. It is relevant to ask why these differences occur, and one pertinent observation is that it is often difficult to show the corpus callosum directly on fetal ultrasonography; therefore, clinicians in the field often rely on surrogate anatomical indicators of its presence. Leading amongst those is the cavum septum pellucidum (CSP), which is said to be absent in ACC in most textbooks on fetal ultrasonography. Conversely, examples of the conditions that feto-maternal experts consider if the CSP is not seen on fetal imaging include: anencephaly, holoprosencephaly, septo-optic dysplasia, ACC, isolated absence of the CSP, any extensive destructive process of the brain (e.g., hydranencephaly), and destruction of the CSP secondary to raised intraventricular pressure, i.e., hydrocephalus.
The latter two scenarios imply that the septum pellucidum did form normally but was destroyed at a later stage, while the other developmental abnormalities usually implicate non-formation of the septum pellucidum. This point is highly relevant as the reverse of the argument is frequently applied in clinical practice, i.e., if the CSP is seen, the corpus callosum is assumed to be present. The purpose of this paper is to judge if that supposition is true.
Classification of commissural disorders (From reference 9).
I Classical commissural agenesis
A. Complete commissural agenesis
Corpus callosum and hippocampal commissure absent
Anterior commissure absent in 50%, present in 50% (small or normal)
B. Partial commissural agenesis
Corpus callosum: typically the posterior portion is variably absent; rarely the agenesis may affect the genu instead of the posterior part of the corpus callosum
Hippocampal commissure is absent
II Commissural agenesis with meningeal dysplasia
Partial or complete absence of the commissures
Presence of multiloculated, non-communicating cyst within the meninges of the interhemispheric fissure, not communicating the ventricular lumen. Extensive deformity of the brain due to mass effect of the cyst
Parencyhmal disorders such as dysplastic cortex bordering the cysts and masses of heterotopic gray matter
III Agenesis of a single commissure
A. Corpus callosum agenesis
1 Complete agenesis
2 Partial agenesis
More common than complete agenesis
The intermediate portion of the corpus callosum is lacking, whereas the anterior portion and splenium are present
B. Hippocampal commissure agenesis
C. Anterior commissure agenesis
IV Other commissural dysplasia
Hyperplasia (associated with neurofibromatosis I)
V Septo-commissural dysplasia
A. Septo-optic dysplasia with partial commissural agenesis
In 25% of cases of septo-optic dysplasia, a partial agenesis of the commissures is associated with the septal agenesis and the anterior optic defects
B. Septo-optic dysplasia with complete commissural agenesis or septo-commissural agenesis
No bundle of Probst and no sheath of white matter closing the medial aspect of the ventricles. Instead, the ventricle is closed with tela choroidea, which may expand as an interhemispheric cystic cavity continuous with the ventricles
In “agenesis” of the corpus callosum, the crossing fibers are not actually absent, they merely stay within the ipsilateral hemisphere as the bundles of Probst.
The fornices are invariably present in cases of agenesis of the corpus callosum as the fornix forms much earlier in fetal life than the corpus callosum.
The septum pellucidum is a paired, parasagittal structure in the fetus linking the fornix to the axons of the corpus callosum.
On this analysis, the septum pellucidum should be present in ACC although not in its normal position. In order to study this further, we have investigated the relationship between the bundles of Probst and the fornix in cases of failed commissuration: Is there any structure that links the two that could be designated “septum pellucidum”? For this, we have reviewed 18 children who underwent MR imaging at Sheffield Children's Hospital for clinical purposes and were shown to have either classical commissural agenesis or commissural agenesis with meningeal dysplasia according to Raybaud's classification. This included eight cases of complete commissural agenesis (type IA), six with partial (type IB), and four with associated meningeal dysplasia (type II). All had the same high-resolution MR examination that included T1-weighted volume imaging acquired with 1.0-mm partitions acquired at 1.5 T.
Complete classical commissural agenesis
Partial commissural agenesis
This covers a wide spectrum of abnormalities. We included the mildest form (absence of the rostrum) in our first paper discussing normal and near normal appearances as the small number of cases we have seen have been in normal volunteers. At the other extreme, we have studied five cases in which the majority of the corpus callosum was missing, and we show the MR imaging of one child in which only the genu and a small portion of the body were present (Fig. 3). In all of those cases, the posterior trajectory of the fornix was the same as in ACC, the fornix contacting the bundle of Probst. As the fornix turns anteriorly, there was clear separation between the fornix and the bundle of Probst just behind the hypoplastic corpus callosum with thickened leaves of the CSP clearly shown (Fig. 3c). Those structures were also demonstrated underneath the hypoplastic corpus callosum (Fig. 3d) where the two leaves remain separate. The passage of the fornix around the anterior commissure appeared to be normal but the CSP was in continuity with the anterior inter-hemispheric fissure because of the absence of the rostrum.
Commissural agenesis with meningeal dysplasia
Implications for fetal imaging
ACC suspected on ultrasonography and confirmed on iuMR.
ACC suspected on ultrasonography but not shown on iuMR.
ACC shown on iuMR when the fetal brain was being investigated for reasons other than ACC.
Between 2004 and 2007, we performed 50 iuMR examinations on fetuses with ACC suspected on ultrasonography. ACC was confirmed by iuMR in 32 of 50 (64%) and refuted in 18 of 50 (36%). During the same period, we studied 136 fetuses referred for iuMR as part of a study of fetuses diagnosed with isolated ventriculomegaly on ultrasonography. ACC was present as an unexpected finding in 11 of 136 of cases (8%) and constituted the largest group of disagreements between the two techniques (manuscript in preparation). We believe that this indicates the breadth of the problem in our practice although we acknowledge that other groups maintain that their figures of misdiagnosis of ACC are lower (in some cases considerably lower or non-existent).
If we accept that iuMR has a role in the pre-natal diagnosis of brain malformations, and in particular, if it is helpful in diagnosing ACC, then we need to consider why. Current iuMR methods produce images with a lower anatomical resolution than ultrasonography but better contrast resolution in most situations. The ultrasonographic appearance of the CSP is highly characteristic, two hyperechoic stripes on either side of the midline and its presence is often taken to imply the presence of a normal corpus callosum. When sagittal images of the fetal brain cannot be obtained with ultrasound (e.g., in cases with unfavorable lie of the fetus or if the mother has a high body mass index), it will be difficult to obtain good views of the full length of the corpus callosum, but this is rarely a problem for iuMR.
In summary, review of the embryology of the cerebral commissures, septum pellicidum, and fornix does not reveal any reason why the septum pellucidum should be absent in cases of ACC. We have shown that children with ACC or hypoplasia of the corpus callosum have a structure that links the fornix and bundles of Probst, and that should be recognized as the deformed leaves of the septum pellucidum. It is highly likely that in some cases those structures would be detected on antenatal ultrasound leading to a false assumption that the corpus callosum is normal.
Conflict of interest statement
We declare that we have no conflict of interest.