2006-06-08-14 Fetal valproate syndrome © Cuillier www.thefetus.net/

* Department of Gynecology, Félix Guyon Hospital, ** Sonographer, Moufia street *** Department of Neonatology, Hôpital Félix Guyon **** Department of Gynecology, Intercommunal"Hospital,  Reunion Island, France

Definition: A cystic mass in the posterior fossa has been described as a pathological finding correlated to Dandy-Walker malformation, vermian cerebellar hypoplasia Dandy-Walker variant or mega cisterna magna (1,2).

Dandy-Walker malformation is characterized by the ascent of the cerebellar tentorium with ventriculomegaly of variable degree. It results in a large cisterna magna. This anomaly is frequently associated with chromosomal anomalies. A defect in the cerebellar vermis and a communication with the fourth ventricle may be also present.

In Dandy-Walker variant, there is a variable hypoplasia of the cerebellar vermis with or without an enlargement of the cisterna magna. Vermian cerebellar hypoplasia is easy to diagnose, even when the large cisterna magna is not present.

Mega cisterna magna is an enlarged cisterna magna with integrity of both cerebellar vermis and fourth ventricle. Nevertheless, the diagnosis of a cystic lesion in posterior fossa often leads to a difficulty in the diagnosis. Indeed the fluid nature is easy to discovered, but sometimes it is really difficult to differentiate Dandy-Walker variant, Dandy-Walker syndrome and mega cisterna magna. We describe a case of mega cisterna magna associated with valproic use and rocket bottom.

Case report: A 30-year-old woman, G2P1, was referred at 32 weeks. At 13 weeks, the nuchal translucency was normal. Biochemical screening for Down syndrome at 17 weeks was normal. A detailed scan at 22 weeks  was also normal. The woman has been taken regularly three anti-epileptic chemotherapy (Valproic acid, Phenobarbital and lamotrigine).

At 32 weeks, a mega cisterna magna was diagnosed. The cisterna magna measurement was 14 mm. The cerebellar vermis and the lateral ventricles were normal. The right foot was in an equine position and there was a rocker bottom on the left feet. An amniocentesis was performed. The karyotype was 46 XX. All the serology tests were negative (Toxoplasmosis, Rubeola, CMV). After counseling, the parents decided to continue the pregnancy. The cerebral anomaly did not progress during the pregnancy. A MRI was performed and confirmed the diagnosis. The baby was born at 38 weeks (3500g). The external morphology analysis of the baby was normal, except the feet anomalies. The transfontanellar scan confirmed the isolated mega cisterna magna. At one month of life, the clinical examination of the baby was normal.

Scan at 31 weeks showing the large posterior fossa

Mid-sagittal view showing the corpus callosum and the cisterna magna

3D view at 33 weeks showing a right club foot

MRI at 31 weeks confirming the enlargement of the cisterna magna

History: Mega cisterna magna is classically described nowadays as an isolated ultrasound finding. Nevertheless, Lai et al (2002) described the antenatal diagnosis in fetus with a trisomy 21 without any cerebellar hypoplasia associated.

Prevalence: An enlarged cisterna magna is seen around 1% of all brains studied postnatally (2).

Etiology: Enlargement of the cisterna magna has been reported in cases associated with chromosomal abnormalities (such as trisomy 18 and 21 or sex chromosomal rearrangement), posterior fossa cysts, cerebellar hypoplasia, Dandy-Walker variant and communicating hydrocephalus. An enlarged cisterna magna has also been associated with infarction, inflammation and infection, particularly CMV (4). Contrary, reduction of the size or disappearance of the cisterna magna has been reported in Arnold-Chiari malformation. However, when isolated, the enlarged cisterna magna is not a valuable marker.

Pathogenesis: The cystic lesions of the posterior fossa result to a large extent from the complex development of the ventricular system and its communication. The rhombencephalon stretches rapidly with a subsequent anterior curvature (pontic flexure) leaving a large posterior cavity. Mega cisterna magna is considered to be a normal variant, corresponding to an expansion of the inferior cerebellar lack (or big cisterna), with free communication with peri-medullar arachnoidea space (2).

Sonographic findings: In routine practice, a normal posterior fossa is assessed by an axial plane at the level of the cerebellar hemispheres. A normal cisterna magna does not exceed 10 mm in depth. A normal transverse cerebellar diameter and a normal cerebellar anatomy (with a distinct vermis surrounded by two normal hemispheres) must be seen. Routinely, the cisterna magna is measured during the second trimester. The evaluation is, however, reported to be difficult during the third trimester, because of attenuation of the ultrasound due to the skull mineralization (4). Nevertheless, it is also known that some fetuses showing posterior fossa abnormalities can be considered variants of the normal, called mega cisterna magna, which has a favorable neurological prognosis (5).

Scan of the posterior fossa in an angled semi-coronal plane should be avoided because it can mimic an abnormality such as cisterna magna or Dandy-Walker Variant. Sometimes linear echoes within the cisterna magna are seen, particularly if the cisterna magna measured more than 3 mm. These echoes correspond to dural folds which probably represents the inferior attachment of the falx cerebri. They are absent in Dandy-Walker cyst and also in Dandy-Walker variant according to Bernard (2).

Implications for targeted examinations:  Recently, Watanabe et al reported MRI imaging of the development of cisterna magna and the subarachnoid space in the cerebellar hemispheres and in the posterior fossa (4). The cisterna magna is measured from the middle posterior aspect of the cerebellar vermis to the internal margin of the cranium on the transverse images. According Watanabe et al, their studies showed a positive correlation between the size of the posterior magna and gestational age (4). The clinical significance of the size of the cisterna magna has been reported by different investigators and abnormal findings have been reported to be associated with various disease.

Differential diagnosis: The main differential diagnosis of cisterna magna should sbe performed before 18 weeks when a non-closure of the vermis is still physiological. After this age, the differential diagnosis includes a Dandy-Walker malformation, vermian cerebellar hypoplasia Dandy-Walker variant or mega cisterna magna (5).

Associated anomalies: Mega cisterna magna is usually isolated, but Guibaud et al described the prenatal antenatal diagnosis of an isolated extra cerebellar ectopic brain tissue, confirmed by MRI (4).

Prognosis: According to different authors, the prognosis of mega cisterna magna is correlated with the anatomy of the vermis as well as the associated cerebral malformation. The posterior fossa is an excellent landmark for fetal anomalies. Particularly it may help to diagnosis spina bifida, when an Arnold Chiari malformation is visible. Conversely, anechoic dilated posterior fossa is a essential clue for the diagnosis of Dandy-Walker variant or Dandy-Walker malformation. So when we diagnose a mega cisterna magna, it is essential to perform a karyotype and a detailed fetal examination to look for associated anomalies that could affect the prognosis. Nevertheless an unusually anechoic aspect of the posterior fossa seems with good prognosis.

Management: Therefore, after the diagnosis of a mega cisterna magna an accurate anatomical imaging of the posterior fossa (particularly to identify the vermian fissures) is recommended. 

References:
1- Bronshtein M., Zimmeer E.Z., Blazer S.- Isolated large fourth ventrcile in early pregnancy – a possible benign transient phenomenon. Prenat Diagn 1998 ; 18 : 997-1000. 2- Bernard J.P., Moscoso G., Renier D., Ville Y.- Cystic malformation of the posterior fossa. Prenatal Diagn 2001 ; 21 : 1064-9.
3- Lai T.H., Cheng Y.M., Chan F.M.- Prenatal diagnosis of trisomy 21 in a fetus with enlarged cisterna magna. Ultrasound Obstet gynecol 2002 ; 413-416.
4- Guilbaud L., Des Portes V.- Plea for an antomical approach managment of the posterior fossa in prenatal diagnosis. Ultrasound Obstet Gynecol 2006 ; 27 : 477-81.
5- Yukiko Watanabe, Seiji Abe, Kenjiro Takagi, Tatsuo Yamamoto, Toshinori kato- Evolution of subarachnoid space in normal fetuses using MRI. Prenatal diagn 2005 ; 25 : 1217-22.
6- Chen C.P., Shih J.C.- Prenatal diagnosis of bilateral ventriculomegaly and an enlarged cisterna magna in a fetus with partial Trisomy 9 and partial trisomy 21. Prenatal Diagn 1999 ; 19 : 1175-80.
7- Guibaud L., Devonec S., Des Portes S., Roth P., Gaucherand P., Pracros J.P.- Pictures of the month. Extracerebellar ectopic brain tissue in the posterior fossa. Ultrasound Obstet Gynecol 2005 ; 26 : 687-9.