Congenital subependymal pseudocysts: own data and meta-analysis of the literature.

Background: Congenital subependymal pseudocysts are incidental findings that are found in 0.5±5.2% of neonates during postmortem examination or head ultrasonography. In our institution we detected 10 neonates with CSEPC. Objective: To investigate associated etiological factors, morphologic characteristics and outcome of CSEPC. Methods: We performed a meta-analysis of the literature on CSEPC (1967±98), including our 10 cases. Results: A total of 256 cases of CSEPC were analyzed. Ultrasound diagnosed 77.6% of CSEPC; 48.8% were bilateral and 53.4% were located in the caudothalamic groove or head of caudate nucleus. Altogether, 93.5% resolved during 1±12 months of ultrasonographic follow-up. Compared to the general neonatal population, the following features were more prevalent in the CSEPC population: prematurity, maternal vaginal bleeding, preeclamptic toxemia, intrauterine growth restriction, asphyxia, fetal cytomegalovirus and rubella infections, congenital malformations, chromosomal aberrations, infant mortality, and neurodevelopmental handicap. The risk for neurodevelopmental handicap was significantly higher when CSEPC were associated with fetal infections, IUGR, malformations and chromosomal aberrations, or persistence of CSEPC during follow-up. CSEPC infants without any of these four conditions had a low risk for neurodevelopmental handicap. Conclusions: CSEPC are morphologic features of various underlying conditions encountered in the fetus. Association of CSEPC with IUGR, fetal infections, malformations and chromosomal aberrations or persistence of CSEPC indicates a higher risk for future neurodevelopmental handicaps, probably because of the deleterious effects on the fetal brain that are inherent in these conditions. A favorable outcome is expected in the absence of these risk factors. IMAJ 2001;3:178-183 The survival rates of high risk neonates have significantly increased during the last two decades. The use of head ultrasonographic examination has become routine in neonates. Congenital subependymal pseudocyst is an uncommon finding that is diagnosed by ultrasound of the neonatal brain. Prior to 1980, CSEPC were incidentally detected during postmortem examination of neonates [1±6]. Since 1980, the growing use of head ultrasonography in sick neonates has led to increased detection of CSEPC [7±23]. This resulted in mounting interest regarding the etiology and prognosis of this finding. In four large prospective studies, CSEPC was sonographically diagnosed in 0.5±5% of healthy term neonates [10,22], in 5.23% of sick premature infants [9], and in 4.1% of all admissions to the neonatal intensive care unit [16]. It should be emphasized that CSEPC are congenital and could be diagnosed immediately after birth using head ultrasonography. Acquired cysts due to hemorrhage or infarctions that occur after birth are beyond the scope of this study. CSEPC are classified as pseudocysts because they lack the ependymal cell lining or any specific limiting membrane found in true cysts. CSEPC probably result from an intrauterine injury to the vulnerable germinal matrix in the periventricular subependymal area, mostly due to vascular events such as hemorrhage or infarction or due to congenital infection, mainly cytomegalovirus [1±5]. During fetal life, the subependymal germinal matrix zone is relatively large; it becomes smaller at 32±34 weeks of gestation, and any injury to this region in early gestation might subsequently result in a pseudocyst [4]. Histopathological examination of CSEPC reveals the following features: immature and undifferentiated lining cells, buds of immature cells protruding into the lumen, cavities bounded by thick glial meshwork, subependymal fine trabeculae, destruction of cells, non-homogenousmatrix,macrophages, and iron staining representing an old hemorrhage in some cases [4]. Macroscopically, CSEPC are seen as isolated large cavities that are limited by pseudo-capsules, or as bilateral symmetrical cavities or irregular thin trabeculated honeycomb-like cavities [4]. Sonographically, CSEPC could be unilateral or bilateral, single or multiple. Although CSEPC might be located throughOriginal Articles CSEPC = congenital subependymal pseudocysts * This study was presented in part at the annual meeting of the European Society for Pediatric Research, Belfast, September 1998, and was part of Dr. Osnat Zmora's thesis for fulfillment of the requirements for M.D. degree at the Rappaport Faculty of Medicine, Technion, Haifa. 178 I.R. Makhoul et al. IMAJ . Vol 3 . March 2001 out the periventricular area, they are usually seen in the caudothalamic groove or adjacent to the head of caudate nucleus [Figure 1]. Since CSEPC develop within the germinal matrix, and given that this matrix gradually resolves during fetal life, we speculate that the location of CSEPC might indicate the timing of injury, i.e., the further from the caudothalamic groove the earlier the injury occurred in fetal life. Among sick neonates admitted to our neonatal intensive care unit in 1990±97, we found 10 neonates with CSEPC as demonstrated by head ultrasound. Published reports of CSEPC include rather small series of patients, and each alone is insufficient as a source of information regarding the etiology, associated perinatal factors, morphologic characteristics and outcome of CSEPC. In order to obtain a more comprehensive picture of this condition, we performed a meta-analysis of reports of CSEPC in the literature. Methods Our data During an 18 month period (1996±97), we prospectively performed head ultrasonographic examinations during the first 36 hours of life on all 340 sick neonates admitted to our NICU using a 5-MHz transducer (Model SSD-620, ALOKA Co., Japan). CSEPC were detected in eight neonates (2.3%), a rate that conforms with that of Yamashita et al. [16], in all NICU admissions. Two additional CSEPC cases were found by a retrospective review of the charts of all admissions to the NICU during 1990±96. CSEPC detection rates in the two periods differed because in the years 1990±96 head ultrasound was performed only for sick neonates with suspected neurological abnormalities, while during 1996±97 routine bedside ultrasound was feasible in the NICU and all admitted neonates were screened ultrasonographically for brain abnormalities. We collected relevant data on our 10 neonates with regard to their perinatal course, possible fetal infection and abnormal findings on physical examination. All 10 infants underwent neurodevelopmental assessment at 2±18 months of age. Meta-analysis of literature on CSEPC We conducted a thorough review of the literature on CSEPC in terms of the reported neonatal, radiological and neurological characteristics of this lesion (Medline search, EBSCO Publishing, National Library of Medicine, 1966±99). We found 23 reports consisting of limited series of CSEPC and describing a total of 246 CSEPC cases [1±23]. These reports were either prospective or retrospective and included different sub-populations. In the prospective studies all admitted neonates were sonographically screened for brain abnormalities, including CSEPC. Some of these studies were carried out in the normal nursery, but the majority was performed in the NICU. In the retrospective studies, cranial ultrasound had been performed only for very sick neonates and their records were reviewed for brain sonographic abnormalities. We performed a comprehensive summary that included all the cases described in all the reports, to which we added our 10 CSEPC infants; this totaled 256 CSEPC cases in 24 reports. We summarized the data on diverse variables that might be associated with CSEPC, such as gender, multifetal pregnancies, gestational age at birth, maternal and obstetric complications (vaginal bleeding, preeclamptic toxemia and hypertension, polyhydramnion, oligohydramnion), fetal infections, IUGR, asphyxia, malformations and chromosomal aberrations, mode of diagnosis (postmortem, ultrasound or both), and long-term outcome. We also summarized the morphologic characteristics of CSEPC, such as laterality, location, size, and ultrasound results during follow-up of CSEPC. However, in order to obtain a meaningful comparison of the incidence rates of the examined variables between CSEPC cases Original Articles NICU = neonatal intensive care unit IUGR = intrauterine growth restriction Figure 1. Ultrasound scan of brain at 12 hours of age. [A] coronal section showing a subependymal pseudocyst located anterolateral to the frontal horn of the lateral ventricle (arrow); [B] the same finding in a parasaggital section (arrow). A