Schizencephaly

Schizencephaly is a disorder characterized by congenital full-thickness grey matter-lined clefts of the cerebral mantle

Embryonic porencephaly, early

1.5:100,000 births.1

The neuropathological features of schizencephaly are as follows: 1) hemispheric clefts, lined with pia-ependyma, unilateral in about 50% of cases 2) communication of the subarachnoid space with the lateral ventricle medially, with infolding of gray matter along the cleft, and 3) multiple associated intracranial malformations, including polymicrogyria, gray matter heterotopias, absent septum pellucidum, optic nerve hypoplasia and agenesis of the corpus callosum.2-4 Yakovlev and Wadsworth describe two variants of schizencephaly by the presence of "fused" clefts in the cerebral mantle (type I) as opposed to separated clefts of mantle, usually in association with ventriculomegaly of varying degrees (type II).5, 6

Cerebral abnormalities are virtually always present and include cortical malformations, white-matter atrophy, , callosal anomalies and hippocampal anomalies.The septum pellucidum is absent near 50%. The association of schizencephaly and septal and optic pathway anomalies is commonly referred to as septo-optic dysplasia-schizencephaly. One third of infants are found to have extra-cerebral malformations usually of disruptive origin including gastroschisis, bowel atresias, and amniotic band disruption sequence.

The precise pathogenesis of schizencephaly is debated. The original work of Yakovlev and Wadsworth contends that schizencephaly is the consequence of a primary migrational failure of the primitive neuroblasts.5, 6 Recently however there is general consensus that in most cases schizencephaly is a part of the spectrum of encephaloclastic disorders that also includes porencephaly and hydranencephaly.2, 7, 8.

Although schizencephaly has been associated with genetic conditions such as EMX2 mutation9-11, most cases are though to be the direct consequence of a vascular disruption due to a wide variety of conditions and agents including monozygotic twinning,1 drug assumption (alcohol, cocaine)12, and infections (cytomegalovirus)13,.

Familial cases have been reported and an association with an EMX2 mutation has been described. This however seems to be occur in only in a minority of cases.

Prenatal diagnosis of schizencephaly type II (open lips) has been reported.^14-16 The most striking finding is the presence of fluid filled clefts in the cortex, establishing a communication between the lateral ventricle and the subarachnoid space. Agenesis of the septum pellucidum with fusion of the frontal horns was also noted in several cases. We anticipate that the type I variety would be exteremely difficult to diagnose antenatally. Clefts with fused lips can be identified postnatally by CT and MRI2⁷ but it is uncertain whether this is possible in utero either with MR or sonography.

Schizencephaly occurs very early in gestation. It is therefore likely that the cerebral clefts associated with the type II variety can be recognized by the midtrimester. Absence of the corpus callosum and ventriculomegaly are also frequently present and this would facilitate the diagnosis. An exception could be represented by cases with unilateral clefts involving the cerebral hemisphere proxymal to the transducer that is commonly not seen during standard examinations. It is of note however that most cases thus far have been recognized only in late gestation.

The sonographic findings in fetal schizencephaly may be similar to those encountered with other intracranial abnormalities, such as lobar holoprosencephaly, septo-optic dysplasia and intracranial cysts. The most important clue to the recognition of schizencephaly (at least, the type II variety) is the presence of cortical clefts. For this reason, differentitating an open porencephalic cyst from a schizencephalic cleft may be impossible.

Variable and debated. Motor impairment and mental retardation are the most common symptoms. The severity however depends upon laterality, extent and position of the schizencephalic defect, as well upon the association with other neural and extra-neural anomalies2, 10. Seizures are present in about half of the cases and drug resistant in a third, and do not seem to be related to the severity of the malformation.10

Standard obstetric care. Schizencephaly with large clefts has usually a poor prognosis and a conservative management should be considered.

1. Curry CJ, Lammer EJ, Nelson V, Shaw GM. Schizencephaly: heterogeneous etiologies in a population of 4 million California births. Am J Med Genet A 2005;137(2):181-9.

2. Barkovich AJ, Kjos BO. Schizencephaly: correlation of clinical findings with MR characteristics. AJNR Am J Neuroradiol 1992;13(1):85-94.

3. Hayashi N, Tsutsumi Y, Barkovich AJ. Morphological features and associated anomalies of schizencephaly in the clinical population: detailed analysis of MR images. Neuroradiology 2002;44(5):418-27.

4. Packard AM, Miller VS, Delgado MR. Schizencephaly: correlations of clinical and radiologic features. Neurology 1997;48(5):1427-34.

5. Yakovlev PI, Wadsworth RC. Schizencephalies: a study of the congenital clefts in the cerebral mantle. I: Clefts with fused lips. . J Neuropatol Exp Neuro 1946;5:116-130.

6. Yakovlev PI, Wadsworth RC. Schizencephalies: a study of the congenital clefts in the cerebral mantle. II: Clefts with hydrocephalus and lips separated. J Neuropathol Exp Neurol 1946;5:169-206.

7. Barkovich AJ, Norman D. MR imaging of schizencephaly. AJR Am J Roentgenol 1988;150(6):1391-6.

8. Govaert P. Prenatal stroke. Semin Fetal Neonatal Med 2009;14(5):250-66.

9. Granata T, Farina L, Faiella A, Cardini R, D'Incerti L, Boncinelli E, Battaglia G. Familial schizencephaly associated with EMX2 mutation. Neurology 1997;48(5):1403-6.

10. Granata T, Freri E, Caccia C, Setola V, Taroni F, Battaglia G. Schizencephaly: clinical spectrum, epilepsy, and pathogenesis. J Child Neurol 2005;20(4):313-8.

11. Tietjen I, Bodell A, Apse K, Mendonza AM, Chang BS, Shaw GM, Barkovich AJ, Lammer EJ, Walsh CA.Comprehensive EMX2 genotyping of a large schizencephaly case series. Am J Med Genet A 2007;143A(12):1313-6.

12. Derauf C, Kekatpure M, Neyzi N, Lester B, Kosofsky B. Neuroimaging of children following prenatal drug exposure. Semin Cell Dev Biol 2009;20(4):441-54.

13. Iannetti P, Nigro G, Spalice A, Faiella A, Boncinelli E. Cytomegalovirus infection and schizencephaly: case reports. Ann Neurol 1998;43(1):123-7.

14. Fernandez-Mayoralas DM, Fernandez-Jaen A, Jimenez-De-la-Pena M, Recio-Rodriguez M, Munoz-Jareno N, Arroyo-Gonzalez R. Schizencephaly: pre- and postnatal magnetic resonance imaging. J Child Neurol;25(8):1020-3.

15. Hung JH, Shen SH, Guo WY, Chen CY, Chao KC, Yang MJ, Hung CY. Prenatal diagnosis of schizencephaly with septo-optic dysplasia by ultrasound and magnetic resonance imaging. J Obstet Gynaecol Res 2008;34(4 Pt 2):674-9.

16. Pilu G, Falco P, Perolo A, Sandri F, Cocchi G, Ancora G, Bovicelli L. Differential diagnosis and outcome of fetal intracranial hypoechoic lesions: report of 21 cases. Ultrasound Obstet Gynecol 1997;9(4):229-36.

17. Sonographic examination of the fetal central nervous system: guidelines for performing the 'basic examination' and the 'fetal neurosonogram'. Ultrasound Obstet Gynecol 2007;29(1):109-16.

This article should be cited as: Pilu G, Malinger G, Buyukkurt S,: Schizencephaly. Visual Encyclopedia of Ultrasound in Obstetrics and Gynecology, www.visuog.org (January 2013).

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