Schizencephaly revisited

Abstract

Purpose: In this paper, I will report the range of appearances of schizencephaly in children and fetuses by reviewing a 10-year experience from a single centre and detail classification systems for the different forms of schizencephaly. This will lead to re-assessment of possible aetiological and mechanistic causes of schizencephaly.

Methods: All cases of pediatric and fetal schizencephaly were located on the local database between 2007 and 2016 inclusive. The studies were reviewed for the presence, location and type of schizencephaly, as well as the state of the (cavum) septum pellucidum, the location of the fornices and the presence of other brain abnormalities.

Results: The review included 21 children and 11 fetuses with schizencephaly. Schizencephaly (type 1) was found in 9% of children but no fetuses, schizencephaly (type 2) was present in 67% of the pediatric cases and in 45% of fetuses, whilst schizencephaly (type 3) was present in approximately 24% of children and 55% of fetuses. Other brain abnormalities were found in 67% of children and 55% of fetuses.

Conclusion: I have proposed a new system for classifying schizencephaly that takes into account all definitions of the abnormality in the literature. Using that approach, I have described the appearances and associations of pediatric and fetal cases of schizencephaly from a single centre. Review of the current literature appears to favour an acquired destructive aetiology for most cases of schizencephaly, and I have proposed a mechanism to explain the cortical formation abnormalities found consistently in and around areas of schizencephaly.

Keywords: Fetus; MR imaging; Pediatric; Schizencephaly.

Fig. 1

Classification of the three different types of schizencephaly used in this paper compared with other nomenclature systems with pictorial examples (see text for details)

Fig. 2

A child with porencephaly. MR imaging of an 8-year-old child with spastic quadriplegic cerebral palsy recognised in the first year of life. Axial T2-weighted (a), axial FLAIR (b), coronal FLAIR (c) and coronal inversion recovery (d) show bilateral clefts involving the paracentral lobules, which extend from the outer surface of the brain but do not quite reach the ventricular margin. Some of the white matter next to the clefts is gliotic and there is no evidence of normal, or abnormal, grey matter lining the clefts. These features indicate porencephaly rather than schizencephaly

Fig. 3

Unilateral schizencephaly (type 1). MR images of a 4-year-old child with focal epilepsy. Axial T2-weighted (a), right parasagittal T2-weighted (b), axial (c) and coronal reconstructions from T1 volume imaging show abnormal grey matter extending from ventricular to out surface of the brain, centred on the right middle frontal gyrus. No CSF cleft is visible, hence the classification as schizencephaly (type 1). The septum pellucidum is present and the course of the fornices is normal. No other brain abnormalities are present

Fig. 4

Unilateral schizencephaly (type 2). MR images of a 4-year-old child with focal epilepsy and developmental delay. Axial T2-weighted (a, b) and coronal inversion recovery (c, d) images show a CSF cleft with closely opposed borders lined with polymicrogyria. There is also a small area of gliosis in the white matter of the contralateral paracentral lobule (arrowed on a). The septum pellucidum is absent and the fornices lie abnormally low (arrowed on d). No other brain abnormalities were present

Fig. 5

Bilateral schizencephaly (type 3). MR images of a 2-year-old child with global developmental delay. Axial T2-weighted (a, b) and coronal reconstructions from T1-weighted volume data (c–f) show bilateral CSF clefts with non-opposed borders lined with polymicrogyria. The septum pellucidum is absent and the fornices lie abnormally low (arrowed on c–f). Extensive cortical formation abnormalities were present in both hemispheres

Fig. 6

Two regions of schizencephaly (type 2) in the same hemisphere. MR images from a 2-year-old child with hemiparietic (left side of body) cerebral palsy. Axial T2-weighted image shows schizencephaly (type 2) related to the right paracentral lobule (arrowed on a) whilst the right parasagittal image from a T1 volume acquisition shows a further area of schizencephaly (type 2) in the inferior frontal gyrus (arrowed on b). The anterior part of the corpus callosum is absent and there is a low position of cerebellar tonsils. Coronal reconstructions from the T1 volume data from posterior to anterior (c–f) show an aberrant course of the fornices and distorted, thickened septum pellucidum (arrowed on c, e and f)

Fig. 7

a–d Bilateral schizencephaly (type 2) with an intact septum pellucidum, normal course of the fornices, and no other brain abnormalities in a 3-year-old child with diplegic cerebral palsy

Fig. 8

Bilateral schizencephaly (type 3) with multiple other brain abnormalities. MR imaging of a 5-year-old child with global developmental delay and epilepsy. Coronal reconstructions from T1 volume datasets (a, b) show bilateral schizencephaly (type 3) involving the inferior frontal gyri. Bilateral cortical formation abnormalities are present in the superior portions of the frontal lobes. The corpus callosum and septum pellucidum are absent and the fornices have an abnormal low position (arrowed on b and c). Axial T2-weighted image shows abnormal fusion of the nucleus accumbens septi and basal forebrain across the midline (arrowed on d) which possibly represents a form of septo-preoptic holoprosencephaly

Fig. 9

MR images of a 7-year-old child (upper pane of the images) with bilateral schizencephaly (type 2) and known EMX2 genetic mutation and MR images of a 7-month-old child with a strong family history of schizencephaly but no genetic testing at the time of the MR study (lower pane of the images). The two cases show similar imaging features as discussed in the text

Fig. 10

Unilateral schizencephaly (type 2) in a 21gw fetus. Sagittal (a) and axial (b, c) ultrafast T2-weighted images show a cleft in the right occipital lobe with opposed deep portions (arrowed on b). Subependymal heterotopia was also present (not shown). Those images are reversed to be consistent with the constructed model of the brain (d—right lateral, e—posterior and f—superior) which show the superficial part of the cleft is quite wide. There is a midline meningocoele posteriorly which is well shown on the models of the external CSF spaces (g–i)

Fig. 11

Unilateral schizencephaly (type 3) in a 21gw fetus. Coronal (a) and axial (b) ultrafast T2-weighted images show a widely spaced cleft in the right paracentral lobule. Those images are reversed to be consistent with the constructed models (c—left lateral and d—superior) of the brain constructed from a 3D steady-state acquisition. The septum pellucidum is absent but no other brain abnormality was shown

Fig. 12

Representation of the ependymal/pial pinning theory of schizencephaly. Coronal histology sections of the fetal brain at 10gw (a), 17gw (b) and 28gw (c) illustrate early pinning of the ependymal and pia (arrowed on a) with the development of an ependymal/pial seam. These sections have been reproduced after alteration with permission [23]

Fig. 13

Representation of the destructive theory of the formation schizencephaly. Coronal histology sections of the fetal brain at 17gw (a) have been reproduced after alteration with permission [24]. The red quadrilateral on figure a represents a focal, full-thickness injury to the cortical mantle and resorption of the damaged brain. Neuro-glial migration is still possible at this stage and will form the regions of polymicrogyria in the borders of the schizencephalic cleft. b iuMR images from a fetus imaged on two occasions because of the history of monochorionic pregnancy and selective termination of one twin. Imaging at 21gw shows high signal and loss of volume in the otherwise normally formed posterior portions of both hemispheres. Repeat iuMR at 27gw shows the development of schizencephaly (type 3) in the left posterior hemisphere. This case is not from our cohort but shown courtesy of Professor M. Kilby, University of Birmingham, and has been described elsewhere [25]

Fig. 14

Representation of the destructive theory of the formation of ‘reparative’ polymicrogyria. Coronal histology sections of the fetal brain at 17gw (a) have been reproduced after alteration with permission [24]. The red quadrilateral on a represents a focal, superficial injury to the cortical mantle, and resorption of the damaged brain is shown. Late neuro-glial migration in this case will produce polymicrogyria on the cortical surface. b iuMR images from a 9-week child which resulted from a monochorionic pregnancy complicated by twin-twin transfusion with survival of both twins. Axial T2-weighted and images from a T1 volume study and non-orthogonal along the course of the sylvian fissure show focal polymicrogyria in the abnormal posterior extension of the sylvian fissure (arrowed)