Clinical presentation
SEGA is a WHO Grade I tumor that often occurs in the lateral ventricle near the foramen of Monro and rarely in the third ventricle, the fourth ventricle and pineal region [1–3]. However, the outcome of SEGA may be poor due to obstructive hydrocephalus or intratumoral hemorrhage [4]. Tuberous sclerosis complex has an association with sudden death. Sudden death may be due to epilepsy, cardiac arrhythmia, and intra-tumoral hemorrhage [5, 6]. Some authors reported that SEGA has been no evidence of any recurrence even after subtotal removal. However, some other authors considered that residual lesions tended to develop [3, 7].
SEGA accounts for 1.5% of all pediatric brain tumors [8]. In our study, the mean initial age was 16.4 years (range: 5–32years), and 15 patients were less than 18 years upon initial diagnosis, indicating that SEGA tended to occur in young patients. This was similar to the previously reported cases where the age distribution was in the first two decades of life, with the highest frequency in those 5–13 years old [9–11]. The male to female ratio in our series was 11: 9, which did not show obvious sex bias. However, in the group below 18 years, the male: female was 2:1, which showed a prominent male predilection. One of the previous reports described a slight male predominance, which was the same with our result [12]. These demographic discrepancies between the studies were probably caused by a selection bias because of the small number of cases.
It was generally believed that SEGA had a tendency to arise within periventricular regions often adjacent to the foramen of Monro [13]. In our study, the lateral ventricular location was much more frequent (19/20) than the other ventricular location. The remaining one SEGA was in the third ventricle. This distribution pattern was similar to conventional SEGA [1]. Rarely, parenchymal locations have been described in the brain (Basal ganglia and frontal lobe) [8, 14]. Depending on the location of tumors, the most common symptom was increased intracranial pressure. Although SEGA was thought slowly growing, it always deteriorated due to elevated intracranial pressure [15].
Associations with tuberous sclerosis complex
Other symptom, such as abnormal dermatosis was reported to be associated with TSC. When the clinical sign of Tuberous sclerosis (TS) was obvious, an early diagnosis of SEGA was common. Nevertheless, in cases with no evidence of TS, diagnosis and treatment of SEGA in adult seems to be a challenge. A rare case of an intratumoral and a small intraventricular hemorrhage complicating a SEGA without any signs of TS was reported [16]. Thus, a high index of suspicion and urgent treatment should be also required, when SEGA outside the clinical setting of the TS complex and with some urgent presentations. TSC was an autosomal disease and about 60% cases arise as spontaneous mutations as one feature for SEGA. None of our patients had positive family history for TSC. Before the advances in neuroimaging, the diagnosis of TSC was based on clinical manifestation and histopathological findings (Fig. 3). The classic clinical triad of Vogt included facial angiofibroma, mental retardation, and seizures [17].
Earnest L et al.’s study has been shown that 45% of TSC-affected patients had normal intelligence, 29% had features of “Vogt’s triad” and 6% hadn’t any of three features [18]. In our analysis, only one patient presented with classical Vogt’s triad (case 12). TSC was a disorder of cellular migration and differentiation involving all of the germinal layers. It was manifested by hamartomas formed in skin, CNS and viscera. Facial angiofibromas were presented in approximately 85% of older children and adolescents. Multiple peri/subungual fibromas, pathognomonic of were seen in 15–20% of cases [19], as seen in our cases that all these 4 patients with facial angiofibroma were over 3 years old.
TSC has a high incidence for mental retardation, especially when associated with seizures in children. The earlier the seizures occured, the poorer was the intellectual outcome of the patient [19]. In present series, 2 patients with epilepsy showed poor intellectual development at the age of 4 months and 3 years respectively. Therefore, it seemed some correlations between seizure and intellection.
Imaging features
The major neuroradiological lesions are tubers, SEN and SEGA. Nodules and tumors were both located at the subependymal region. A pathogenetic link between SEN and SEGA has been confirmed. Several studies have showed that there was a continuum from SEN to SEGA. The risk factors of the SEN transformed into a tumor primarily included a diameter above 5 mm, calcification and enhancement after gadolinium administration. Moreover, some studies have showed that all SENs were clonal, had the capacity to proliferate, and behaved as true neoplasms [9]. How to distinguish a tumor from SEN is still difficult especially at an earlier stage when the lesion is very small [20]. There were many studies about signal intensity or dense and contrast-enhancing characteristics suggesting correlations between SEN and SEGA [20]. The uniquely detectable difference between SEN and SEGA was the tendency of the latter lesion to enlarge and to obviously enhance with contrast administration in both CT and MRI image [21]. Cortical tubers were better diagnosed on MRI imaging than on CT scan, and they were low signal intensity in T1-weighted imaging and high signal intensity in T2-weighted imaging [20]. However, some authors suggested that signal intensity and contrast enhancement were not useful in detecting the difference between SEN and SEGA, because they found that some SENs also had slight enhancement on radiological imaging [22]. Therefore, the clinical criteria were more important than radiological images in diagnosis. If patients had hydrocephalus or high intracranial pressure, the perimonro lesion could be diagnosed as a tumor [6]. When a lesion near monro was not big enough to diagnose as a tumor, serial follow-up was essential [20]. With the growth of lesion on serial MRI image, the diagnosis of tumor could be made easily. We agreed with the criteria put forward by Cuccia at 2003 which included presence of hydrocephalus, interval increase in tumor size, new focal neurological deficit attributable to tumor, and/or symptoms of intracranial pressure [20].
SEGA appeared to arise from SEN on serial imaging, which was present in 88–95% of patients with TSC [13]. The nodule would grow up even with the treatment of gamma knife after 2 years follow-up [6]. Moreover, the lesion seemed more like a tumor because of its obvious enhancement and absence of calcification.
The common sites of SEGA were cerebral ventricles, including third ventricle, fourth ventricle and lateral ventricle. Only a few cases have been reported of SEGA with intra-axial extension in the literature. To our knowledge, only three cases were reported located at cerebral hemisphere [10, 22, 23].
On CT scan, they were well circumscribed, isodense or hyperdense, and were obviously and homogeneously enhanced after injection of contrast medium; on MRI finding, tumors were isointense, hypointense or hypointense within isointense on T1-weighted or FLAIR images, and hyperintense, isointense or hypointense on T2-weighted image or FLAIR images. Being moderate to strongly heterogenous enhancement could be seen on all of the MRI images. Moreover, frequent calcification and ventricular dilatation could be noted.
In differentiating lateral ventricular tumours, the CT density and morphology characteristics were non-specific, and MR signal intensity patterns, which varied from case to case, were also unhelpful in predicting tumour histology. Currently, data available in the literature showed that exact diagnosis of ventricular neoplasms (neurocytoma, ependymoma, subependymoma, SEGA) was hardly possible on the CT and MRI images since nearly every variation of imaging characteristics (hypo- or hyperintense, contrast enhancement, cyst, etc.) may be present or entirely absent in a single case [12]. Ventricular ependymomas were mostly hyperdense with pronounced contrast uptake. On the contrary, subependymomas were hypodense, mostly without enhancement, but occasionally slight or moderate enhancement was noted, and SEGA also displayed hypodense, rarely hyperdense or mixed imaging characteristics and always in significant degree of contrast enhancement [12]. In accordance with previous reports, all showed hypo- or mixed density, but mostly slight to moderate enhancement. Ependymomas, anaplastic astrocytomas and glioblastomas followed the characteristics of the similar extraventricular ones [21]. The imaging features of ventricular neoplasms were non-specific and usually the diagnosis was made after taking the patient’s clinical condition, age and the location of tumors into consideration. We supposed that the diversity of CT or MR image might due to the different histologic contents of the tumor, such as calcification, necrosis or hemorrhage. We thought that more SEGA cases are needed to further evaluate this problem.
Overall, although the appearance of the tumors on CT or MR imaging scans in our patients was initially indistinguishable from that of other lateral ventricle gliomas and central neurocytomas, clinical features including presence in the first or second decade of life, typical location in the periventricular regions adjacent to the foramen of Monro, hydrocephalus in company with raised intracranial pressure and TSC might be a characteristic finding for SEGA.
