2006-05-31-14 Schizencephaly © Cuillier www.thefetus.net/
Cuillier F*, Lemaire P**, Deshayes M**, Fossati P***
* Department of Gynecology, Félix Guyon’Hospital ** Sonographer, Moufia’street *** Department of Radiology, Hôpital Félix Guyon - Ile de la Réunion - France
Definition: An old definition of schizencephaly is “a form of porencephaly characterized by a cyst or cavity in the cerebral hemispheres”. In fact, schizencephaly is a congenital defect due to an abnormal development of the fetal brain. Schizencephaly is certainly an uncommon disorder of neuronal migration, characterized by a cerebrum-spinal fluid-filled cleft, lined by gray matter. The clefts may extend through the entire hemisphere from the ependymal lining of the lateral ventricles to the periphery (pial surface) covering the cortex of some part of the brain. The cleft can be unilateral or bilateral and are commonly located near the pre- or post-central gyri. The gray matter lining can be dysplastic. There are two types of schizencephaly:
Type I: The clefts can be unilateral or bilateral and may be closed (fused lips). In closed-lip (type I), the cleft walls are in apposition, causing obliteration of the CSF space within the cleft.
Type II: The clefts can be unilateral or bilateral and may be separated (open lips). In open-lips (type II), the clefts walls are separated. The CSF fills the cleft from the lateral ventricles to the subarachnoid space that surrounds the hemispheres.
Case report: This is a 30-year-old-woman, G2P1, referred to our antenatal unit due to a hydrocephaly. The triple test and the nuchal translucency were normal. At 21 weeks, a bilateral hydrocephaly was observed. The spine was normal. The cerebellum was visualized. There was no Arnold-Chiari syndrome. The couple was counseled. They refused to perform an MRI or interruption of pregnancy. The serial scans showed a progressive evolution of the brain lesion. The cortical brain seemed present but very thin.
At 36 weeks, a cesarean section was performed due to macrocrania. Few days latter, a CT scan showed a cleft in right temporal-parietal region. A MRI showed a prominent cleft in right temporal-parietal region cleaving the right parietal lobe, extending from cerebral convexity to right lateral ventricle. The two ventricular systems were communicating. Since then, the baby has been hospitalized several times. He does not have any spontaneous movement and he can not swallow.
Brain view at 21 weeks showing the hydrocephaly. The cerebellum seems normal.
Note the cerebral cleft
The drooping choroid plexus in the cerebral cleft
Normal spine and 3D of the brain at 24 weeks
History: Schizencephaly was first described at the end of the XIXth century. The term of schizencephaly was introduced in 1946 by Yakovlev and Waldsworth. They reported a brain lesion due to an abnormal development of the brain and not secondary to the destruction of mature cortex as previously reported in cases of porencephaly.
Synonym: Schizencephaly type I and type II; cerebrum-spinal fluid-filled clef in the brain; abnormal cleft brain; open lip schizencephaly; closed lip schizencephaly; « agenetic porencephaly », « split brain ».
Prevalence: Among neurological cortical malformations, schizencephaly is the most severe restricted disorder. Schizencephaly has an extremely rare prevalence, with an unknown incidence. There is neither sex nor race predilection. In the literature, more than 70 cases of schizencephaly type I have been described, but the exact incidence is still unknown. Schizencephaly type II is more frequent than schizencephaly type I. Schizencephaly is considered as a non-specific risk factor to prematurity. According to Denis et al, 20% of the children born prematurely compared with 10% in the general population.
Etiology: Several theories have been proposed to explain the etiology of schizencephaly. Indeed the exact etiology of schizencephaly remains unclear, some environmental events have been proposed.
Sporadic: is the principal etiology. No specific prenatal events have been identified, but genetic, toxic, metabolic, vascular of infectious etiology can be responsible.
Fetal hypotensive vasculopathy: due to severe bleeding in the first trimester or fetal hemorrhagia by auto-immune thrombocytopenia
Intrauterine infections: early gestational viral infections, viral illness in particular CMV infection
Environmental events do not entirely rule out the possibility of a genetic mechanism. Exceptional familiar cases of schizencephaly have been reported, raising the possibility of an autosomal dominant inheritance with incomplete penetrance and variable expression. There is also evidence suggesting that unilateral schizencephaly can be familiar and probably accounts for previously cases reported as « familial porencephaly ».
Recent studies have linked schizencephaly with a mutated gene called the Homeobox gene EMX2. If the gene EMX-2 is missing or defective, nerve cell growth and migration will not occur normally and lead to the formation of the clefts associated with schizencephaly. In 1996, Brunelli and al reported for the first time the association of a heterozygous mutation in the homeobox gene in seven sporadic cases and schizencephaly
Pathogenesis: Schizencephaly results from an early, focal destruction of the germinal matrix and surrounding brain, before the hemispheres are fully formed. Schizencephaly can occur due to an abnormal neuronal migration from the germinal matrix zone.
Two theories about the etiology of schizencephaly have been described. The main question is whether schizencephaly results from a lack of development of brain tissue or from a destruction of the final formed brain structures. According to Yakovlev, schizencephaly is a primitive malformation because of the brain features including a symmetric bilateral orientation, extension to the ventricle and the persistence of thick cellularly gray, matter along the wall of the clefts. These findings distinguish this diagnosis from porencephaly.
According to other authors, schizencephaly and polymicrogyria are the result of the same cortical damage, because of the frequent association of an unlayered cortex lining surrounding the cleft. Polymicrogyria is attributed to ischemic destruction of the radial glial fibers system that normally guides the migration of the developing neurons. Schizencephaly would be an extreme variant of cortical dysplasia in which the infolding of the cortex extends all the way into the lateral ventricles. The clefts in schizencephaly are lined either totally or in part by gray matter and extent from the pial surface to the ependyma of the lateral ventricle. The cleft can be localized anywhere on the brain, but they are usually localized on the perisylvian regions. The cleft can be unilateral or bilateral and be either symmetric or asymmetric. So the cavity formed in the open-lip type varies in size from small to large and may communicate with the lateral ventricle. The ventricle system may be enlarged, particularly with the open lip form of schizencephaly.
Sonographic findings: Schizencephaly may be suspected by the appearance of focal ventricular dilatation and by visualization of gray matter lined cleft on MRI scan. This space is filled with cerebro-spinal fluid (CSF). In both types, the clefts may be only on one side of the brain (uni hemispheres) or on both sides (bi hemispheric). The prenatal scan may detect progressive destructive changes of vascular insult in the distribution of the middle cerebral artery territory. The abnormality results from an infarction in area of the germinal matrix during the seventh week of embryogenesis. This theory is based on the demonstration of a watershed zone in the gray matter along the lateral ventricle in the area of the germinal matrix. The second etiology to explain is the failure of normal migration of the primitive neuroblast resulting in cerebral cleft. So in the wall of the cleft the cerebral mantle exhibits the hallmarks of the migrational disturbance as, microgyri, cortex and large neuronal heterotopia, visible by MRI. The continuity of the gray matter along the associated cerebral malformation supports this second theory.
Implications for targeted examinations: MRI delineates easily the gray matter lining the cleft, which is the pathognomonic finding of schizencephaly. Imaging studies demonstrated a gray matter cleft through the affected hemispheres with an irregular gray matter-white matter junction. The cortex adjacent to the cleft usually demonstrates cortical dysplasia and MRI can show pachygyria, polymicrogyria and heterotopia which line typically the clefts. But cortical dysplasia can also be seen in the contro-lateral hemispheres with unilateral schizencephaly. MRI can show cortical anatomy detail and cleft. Absence of the sylvian vasculature, abnormal position of the fornix and abnormal corpus callosus, may be seen with MRI. The cavum septum pellucidum is absent in 85% of patient with schizencephaly.
Differential diagnosis: Ultrasound diagnosis depends essentially upon the demonstration of defect in the cerebral mantle in the area of Sylvian fissure and the visualization of a communication between enlarged lateral ventricle and subarachnoid space. The differential diagnosis includes the other anomalies that with CSF filling spaces like:
- Arachnoid cyst: The cyst does not communicate with the lateral ventricles
- Porencephaly: especially in the area of the sylvian fissures, porencephaly can be a diagnostic dilemma.
- Holoprosencephaly: There is a mono ventricular cavity with thalami masses fused and absence of the falx. Midline facial anomalies can be present
- Hydranencephaly: There is a near complete absence of cerebellum, with intact meninges and cranial vault
- Gray matter heterotopia
Associated anomalies: Different anomalies can be associated with schizencephaly:
- Gray-matter heterotopia: are collections of gray matter in abnormal brain locations.
- Arachnoid cyst
- Some individuals affected by schizencephaly, may have an excessive accumulation of cebrebrospinal fluid in the brain and caused ventriculomegaly and the hydrocephaly with macrocrania.
- Absent of the corpus callosus
- The septum pellucidum is absent in 80 % of the patients and may coexist with septo-optic dysplasia.
Prognosis: The clinical features of schizencephaly are extremely variable. The severity is related to the importance of the cleft, but most of the baby and then the children have some grave seizure. Usually the severity of these symptoms is related to the amount of the brain, affected by this anomaly.
Children with unilateral clefts have often hemiparesis, but may also have mild-to-moderate developmental delay. Severity is related to the extent of cortex involved in the defect.
Children with bilateral cleft are tetra paretic with severe mental deficits. They have frequently developmental delay, delay speech, abnormal language skills and corticospinal dysfunction. Netherless the degree of malformation is not related to the severity of epilepsy. Individuals with bilateral schizencephaly may also have microcephaly, associated with mental retardation and partial or complex paralysis, poor muscle tone and spastic quadriparesis. They present with early onset of epilepsy, sever motor delay and abnormality, and frequently blindness, deafness (one third of patients). Sometimes they can have some problems with brain-spinal cord communication.
The prognosis of schizencephaly is catastrophic, but depends essentially on the size of the clefts and the extent of neurological disabilities and the presence of associated lesions. Usually, complications such as chronic and acute infections, failure to thrive and respiratory problems, can be the cause of the death of the affected person. Usually patient with open-lip schizencephaly die at an earlier age than patient with the closed lip form. Sometimes, closed-lip schizencephaly may not present clinically until later during the childhood and may live to early adulthood.
Management: MRI is the best method to differentiate schizencephaly from porencephaly and arachnoid cyst. Precise antenatal diagnosis is essential to counsel the couple about the outcome. No treatment is available for the schizencephaly. Untreated seizures are frequently present (generalized tonic-clonic, partial motor and sensory seizure). The treatment is only symptomatic with physical therapy and drugs to prevent the seizures.
Surgical therapy: In cases of hydrocephaly associated with schizencephaly, a cerebral shunt derivation may be perform to deviate the fluid to another area of the body.
1- Denis D., Chateil J.F., Brun M., brissaud O., Lacombe D., Tontan D., Flurin V., Pedespan J.M.- Schizencephaly : clinical and imaging features in 30 infantile cases. Brain development 2000 ; 22 : 475-82.
2- Briellmann R.S., Jackson G.D., Torn-Broers Y., Berkovic S.F.-