Cuillier F, MD*, Carasset G, MD**, Lemaire P***, Deshayes M***, Pilorget H, MD^#

* Department of Gynecology
** Gynecologist, Saint Clothil clinic
*** Sonogapher, Moufia’street  
^# Department of Neonatology, Hôpital Félix Guyon - Ile de la Réunion, France

Definition: The high-resolution ultrasound machines and the introduction of transvaginal probes for the evaluation of the fetal brain anatomy have permitted the detection of rare pathologies. Subependymal pseudocysts are cerebral cysts, usually located in the wall of the caudate nucleus and in the caudal-thalamic groove, precisely located in the germinal matrix. It can be also called congenital periventricular pseudocysts or subependymal germinolysis cysts. They have been described laterally to the wall of the frontal horn of the lateral ventricles in neonates on the first day of life, suggesting a prenatal origin (1).

They may be due to multiples disorders as hypoxic or ischemic injuries, infection, etc. The periventricular leukomalacia can occur as a final event. Nevertheless, in some patients, subependymal pseudocysts may occur as an isolated condition.

We report an ultrasonographic case of subependymal pseudocysts detected at 32 weeks and confirmed by in utero MRI, with normal postnatal outcome.

Case Report: A 28-year-old woman underwent two ultrasounds at 13 weeks (normal nuchal translucency) and 24 weeks. The triple test was normal. At 32 weeks, she underwent the third sonography. In this scan, a septate aspect of the anterior horn of the two ventricles of the fetal brain was seen. The lateral ventricles were not dilated. The fetal biometry was normal. The cerebral analysis showed normal posterior fossa and normal corpus callosum and its artery.

At 34 weeks, the same anomaly was seen. An intrauterine MRI was performed to further investigate those findings. The frontal horns of the lateral ventricles appeared dilated on T2-weighted sequences. Cysts were found laterally close to the ventricle on axial and parasagittal planes, far from the germinative zone and from the superior and external margin of the lateral ventricle. The signal was compatible with fluid-filled cystic masses. The rest of the fetal brain was normal. T1-weighted sequences showed adequate myelinization. MRI excluded any hemorrhagic process.

Routine serology (HBV, HBC, Herpes, EBV, Parvovirus B19, Rubella, Toxoplasma, HIV and CMV) were normal. The karyotype was also normal. Predisposing risk factors for periventricular leukomalacia (such as non steroidal anti-inflammatory drugs, cocaine abuse, abdominal trauma, vaginal bleeding and preeclampsia) were excluded. Peri ventricular haemorrhage associated with fetal allo-immune thrombocytopenia was also excluded by negative maternal anti-platelet antibodies.

The hypothesis of a single subependymal pseudocysts was suggested without certain. A neurological opinion was requested (Pr Pierre-Khan, Necker Hospital, Paris). According to him, the presence of symmetric bi-temporal lesion will can be created bilateral hydrocephaly.

Nevertheless the couple decide to continue the pregnancy. Spontaneously, normal delivery occurred at 39 weeks and a 4200g healthy baby born with normal APGAR scores. Neonatal neurological examination was strictly normal and the same one month latter. Laboratory data showed a normal coagulation screen and there were no clinical or serological signs of congenital infections. At day three, transfontanellar scan showed ventricles with little broadening of the frontal horn. The temporal horn was normal. Three months later, the cyst disappeared and the ventricle was normal.

Our hypothesis seems to be subependymal pseudocysts or congenital periventricular pseudocysts or subependymal germinolytic cysts.

View at 32 weeks showing a subependymal cyst

Transvaginal scan at 32weeks showing normal cerebellum, corpus callosum and pericallosal artery

Parasagittal view at 34 weeks at the level of the lateral ventricles. Cerebral ultrasound showed bilateral symmetrical areas characterized by cyst on the mild lateral border of the lateral ventricles

Transverse scan at 34 weeks, showing bilateral symmetrical echogenic areas with few microcysts on the mild lateral border of the lateral ventricles without ventriculomegaly.

MRI at the level of the frontal horns of the lateral ventricles. Bilateral high signal intensity lesions can be visualized.

MRI at the level of the frontal horns of the lateral ventricles

Parasagittal sonography at 35 weeks

History: Subependymal pseudocysts were described by Banker et Larroche in 1962. Due of the absence of epithelial lining of the cyst wall, the authors suggested that these were pseudocyst (1). The first sonography diagnosis in a neonate is attributed to Levene, in 1981 (2).

Prevalence: The true prevalence of subependymal pseudocysts in newborns is unknown. Subependymal pseudocysts are cerebral cysts found in 5,2 % of all neonates, using transfontanellar scan in the first day of life (3). They are commonly diagnosed in preterm newborns because of the frequent use of cranial ultrasound in this population. Subependymal pseudocysts have been found in newborns admitted to intensive care units (2,5%) and also in neonates referred for cranial ultrasound for other reasons (1).

Etiology: In the vast majority of cases, a simple persistence of the germinal matrix is proposed to explain the subependymal pseudocysts in asymptomatic preterm neonates.

• Viral infections (CMV and rubella) are commonly described, but are associated with other abnormalities of the central nervous system like multiventricular cysts.
• Congenital infection in theses cases could be high as 35%.
• Subependymal hemorrhage is often associated with subependymal pseudocysts and theses cysts often contains calcifications
• Vascular disorders
• Chromosomal deletions: are often associated with impaired neuronal migration (Delq6 ; Delp4)
• Maternal consumption of cocaine
• Metabolic disease with impaired neuronal migration: Zellweger Syndrome, holocarboxylase synthetase deficiency

Pathogenesis: At 4 weeks, the neural tube is a large cavity. The hemispheres and the cortical mantle are formed by 8 weeks. Neurogenesis occurs up to 32-34 weeks and neuronal migration occurs between 26 and 34 weeks.  At birth there are few germinal cells.

The pathogenesis of these subependymal pseudocysts is unclear and results from a persistent germinative zone, which normally disappears when the baby is normally delivered. This could explain why they are found frequently in preterm neonate. Subependymal pseudocysts are thought to be a result of antenatal cyst matrix regression of germinolysis and they probably occur following hemorrhage or microinfarction of the germinal matrix. Fluctuations in systemic pressure may cause germinal matrix hemodynamic of multifocal periventricular necrosis. The germinal matrix is supplied by capillaries, which are vulnerable to sudden haemodynamic changes. Injury to the radial cells of germinal matrix before 26- 28 weeks may be expected to interfere with residual neuronal migration and to affect myelinogenesis with serious functional consequences.

Sonographic findings: Subependymal pseudocysts have been rarely described on antenatal period. Subependymal pseudocysts are isolated in 50% of cases. They are usually large and well-limited hypoechoic cavities. MRI typically shows a high density in T1-weighted sequence and a low signal in T2 weighted sequence. Mallinger et al (2002) described the first series (11 fetus affected) (1). They confirmed the good prognosis in children with isolated subependymal pseudocysts, suggested by Makhoul et al, in 2000 (4).

Implications for target examinations: Subependymal pseudocysts are isolated in up to 50% of cases. MRI shows a high intensity in T1-weighted sequences and a low signal in T2-weighted sequences. Isolated subependymal pseudocysts are typically bilateral and more or less symmetrical. They are usually located in the periventricular area, caudal-thalamic and at the head of caudate. They have a good prognosis and regress spontaneously during the year after birth (1).

Atypical subependymal pseudocysts are often periventricular (congenital infection) or near the caudate nucleus (cocaine-exposed neonates). Atypical subependymal pseudocysts carry a poor prognosis depending essentially on the underlying etiology and associated anomalies (3). Subependymal pseudocysts are usually found in the neonatal period, but can be diagnosed in utero. Nevertheless antenatal and neonatal subependymal pseudocysts are the same entity and carry the same prognosis (1).

Differential diagnosis: Subependymal pseudocysts must be differentiated essentially from periventricular leukomalacia cysts because of their completely different prognosis. Subependymal pseudocysts develop in the reminiscent of the germinal matrix, where there are no axons, while periventricular leukomalacia cysts develop in the periventricular unmyelinated white matter especially affecting the corona radiata and centrum semiovale (1).

Associated anomalies: Accordingly to the etiology.

Prognosis: The neurological outcome is related to the extension and localization of the lesions. Increasing size of the cyst is associated with increasing risk of cerebral palsy and all infants with cysts larger than 20 mm diameter have cerebral palsy (6). Parietal-occipital lesions extensively involving the centrum semiovale and the trigone of the lateral ventricles may be associated with moderate to severe motor disabilities within a few months of life. Some observations suggest that germinal matrix hemorrhages resulting in small periventricular cavitations or isolated frontal leukomalacia may be expected to resolve without any neurological impairment. According to the pediatric experience, the prognosis is related to the underlying maternal or fetal etiology causing the lesions as well as the location and the size of the cysts. Small lesions (< 2 cm) located below the frontal horns seems to have a good prognosis as compared to those located in the peritrigonal region (1). When subependymal pseudocysts are isolated and typical, they result form persistence of the germinal matrix and have a good prognosis and regress spontaneously within a few month.

A poor prognosis is related to the presence of additional findings in the brain and others organs. However, associated cerebral or morphologic abnormalities carry a poor prognosis as they are suggestive of vascular disorders (hemorrhage of infarction), infections (CMV, Rubella) or chromosomal abnormalities. The neurological outcome is poor in these cases.

Management: Diagnosis, clinical significance and outcome of prenatal subependymal pseudocyst are necessary for parental counseling and obstetric management. The detection of a prenatal brain injury may have remarkable medico-legal implications. When subependymal pseudocyst is seen in the prenatal period, it is necessary to search for pathological maternal conditions which can cause ischemic hemorrhagic lesions of the brain (preeclampsia, IUGR, thrombocytopenia, trauma, drug abuse, congenital infections, etc.). The prognosis depends from underlying pathology and from extent of the cystic lesions. When no cause is identifiable and the cysts are located below the frontal horns the prognosis is good.

About our case, the parents were advised that an hydrocephaly can occur latter or another neurologic complication. According to Ramenghi (2005), congenital thrombophilia should be investigated in infants with idiopathic prenatal germinal matrix intra-ventricular hemorrhage, having excluded maternal trauma and the most common hemorrhagic diseases.

References:
1- Malinger G., Lev D., Ben Siras L., Kidron D., Tamarkin M., Lerman-Sagie T.- Congenital periventricular pseudocysts : prenatal sonographic appearance and clinical implications. Ultrasound Obstet Gynecol 2002 ; 20 : 447-51.
2- D'Addario V., Selvaggio S., Pinto V., Resta M ;, Di cagno L., fama A.- Fetal subependymal cysts with normla neonatal outcome. Fetal diagn Therapy 2003 ; 18 : 170-3.
3- Bats A.S., Molho M., Senat M.V., paupe A ;, Bernard J.P., Ville Y.- Subependymal pseudocysts in the fetal brain : prenatal diagnosis of two cases and review of the literature. Ultrasound Obstet Gynecol 2002 ; 20 : 502-5.
4- Makhoul I.R., Zmora O., Tamir A., Shahar E., Sujov P.- Congenital subependymal pseudocysts : own dta and meta-analysis of the literature. Isr med Assoc J 2001 ; 3 : 178-83.
5- Malinger G., Katz R., Amsel S., Gewurtz G, Zakut H.- Brain, hemorrhage, gerimnal matrix. http://www.thefetus.net/
6- Ramenghi L.A., Fumagalli M., Righini A., triulzi F., Kustermann A., Mosca F.- Thrombophilia and fetal germinal matrix-intraventricular hemorrhage : does it matter ? Ultrasound Obstet Gyneco ; 2005 ; 26 : 574-6.