Intracranial Ependymomas in Children the Role of Surgery and the Adjuvant Therapy

Ependymomas are neuro epithelial tumours derived from a neoplastic transformation of ependymal cells that line the ependymal cavity and take part in the glial group of tumours representing 2-9% of all intra cranial tumours and more than 12% of intra cranial tumours in children. 75% of these tumours are located in the posterior cerebral fossa [1-3]. The first histological description of ependymomas was performed by Virchow in 1864. Bailey and Cushing in 1926 classified ependymomas among the glial tumours [1]. Ependymomas of the posterior cerebral fossa affect particularly young infants, whereas the supra tentorial location affects older children, adolescents and adults [1-3]. These tumours manifest clinically with a high intra cranial pressure cerebellar syndrome and focal neurological symptoms. The insertion of posterior fossa ependymomas adhere to the floor of the 4th ventricle (in 80%) and more precisely in the bulbar triangle in contact with vital neurological structures. In this location, ependymomas can develop through the magendie hole to gain size in the cervical subarachnoid space or toward the ponto cerebellar angle and distal cranial nerves through the luschka hole. The upward extension toward the 3rd ventricle is exceptional through the sylvius aqueduct. Their treatment is surgical and can be completed by radiotherapy and/ or chemotherapy as an adjuvant therapy [2-5]. In addition to the problem of the extent of resection, which is usually incomplete due to their location, the prognostic of ependymomas is difficult to predict due to their risk of recurrence and the possibility of distant metastatic implantation through CSF pathways [5]. Radiotherapy has an important role in the treatment of recurrent ependymomas as well as the anaplastic types [2,6].

We are presenting a retrospective study of 56 patients operated in the period between 2015 and 2020 at cherchell specialized hospital in Algiers. Female predominance was found in our serie (29 females and 27 males). The mean age was 8 years with extremes varying from 3 months to 15 years.

Location

The infratentorial location of intracranial ependymomas in children was found in 36 cases (67.8%) whereas the supra tentorial location concerned 18 patients (32.2%). In detail, the infra tentorial location reflects many precise locations of these tumours (Table 1):
a. 18 cases of ependymomas of the floor of the 4th ventricle (Figure 1).
b. 4 cases of ependymomas with extension toward the bulbo medullar junction and the second cervical vertebra.
c. 12 cases of the roof of the 4th ventricle.
d. 7 cases of the lateral recess with extension toward the homolateral cerebellar pontine angle (Figure 2).

Table 1. Number of the main clinical symptoms. Clinical features are multiform.

Figure 1: a, b: Preoperative MRI in sagittal and axial views show an important ependymomas of the Posterior cranial fossa with cisternal extension. c: Early post-operative CT scan showing the extent of the tumour removal after Radiotherapy. d: Image of cervical MRI in sagittal view show a cervical ependymoma in the same patient after 3years follow-up.

Figure 2: a, b: preoperative CT scan showing an ependymoma of the roof of the 4th ventricle with extension toward the cerebello pontine angle. c: MRI in sagittal view showing the quality of resection after radiotherapy and two years follow up.

The supra tentorial location involved
i. 11 cases of lateral ventricle (Figure 3).
ii. 1 case was para ventricular.
iii. 6 cases were para and intra ventricular (Figure 4).

Figure 3: CT scan of intraventricular ependymoma (a) and the extent of the resection after 4 years follow up (b).

Figure 4: Preoperative CT scan (a) of an intra ventricular ependymoma and post-operative image showing the resection quality (b).

Extent of tumour removal

Post-operative imaging (CT scan and MRI) were used to assess the extent of the tumour removal. The majority of our patients underwent CT scan immediately after surgery (Table 2). MRI was performed after a few weeks to evaluate the extent of the tumour resection. The Gros total resection was achieved in 42.8% of patients (25 cases), whereas 25 others had a subtotal resection of infra tentorial locations of the studied ependymomas in Children.

Table 2. Patients features with treatment modality.

Histological grade

More than half of tumours were ependymomas myxopapillary or sub ependymomas of grade I and II of the WHO classification of CNS tumours. 12 cases were grade I and 18 were grade II. The grade III anaplastic ependymomas were found in 44.6% of cases (25 cases).

Adjuvant treatment

More than half of our patients (55.3%) have had radiotherapy as a complementary treatment initially, whereas 21.4% of them received chemotherapy. 4 children received both radiotherapy and chemotherapy.

Morbidity

In the post-operative period, we have recorded complications listed below:
i. 6 cases of CSF fistula after surgery of 6 cases of infra tentorial ependymomas. 4 cases presented meningitis and were treated with targeted antibiotics.
ii. One case presented with a cervical metastasis was réoperated few months after the first surgery with anatomo pathological finding showed an ependymoma.
iii. Two patients presented with post-operative intra cranial pressure due to mal function of VP shunt, they improved after revision.

Prognostic

All our patients were followed up regularly after 36 months especially those for which the tumour removal was nor complete and who have had radiotherapy or chemotherapy. The residual tumour was unchanged and was followed up by oncologists and neurosurgeons. Two cases of supratentorial ependymomas show a late recurrence and were re operated on with an adjuvant chemotherapy. 4 cases of mortality were recorded in the period of 38 months after surgery.

The intra cranial ependymomas represent the third more frequent tumour of the central nervous system in children. Although these tumours can affect patients of every age, 50% of intra cranial ependymomas involve children under 5 years old affecting particularly the infra tentorial compartment in 70-80%. The intracranial ependymomas affects the supra tentorial compartment in adults [6-8]. In our Serie, the infratentorial location was found in 67.8%. in the infancy, Ependymomas are particularly malignant which is different from tumours diagnosed in older children of 10- 15 years of age which have a lower grade. The surgical removal of ependymomas is difficult due to its close relationship to the brainstem, cranial nerves. This feature reflects a dilemma between a total resection with a high risk of morbidity and partial resection with high risk of recurrence and a good post-operative outcome. Many studies argue that the total resection offers a better longterm control. Ikezaki [9] consider that the location and the size of infra tentorial ependymomas were important factors for long term prognosis. The infratentorial ependymomas are then classified into: ependymomas of the roof, floor and the lateral recess of the fourth ventricle. In the latter, the tumour encases cranial nerves IX, X, XI, XII and adhere to the brainstem [10].

The majority of authors agree that the anaplastic type has a poor prognosis whereas the prognosis is variable for the other types of ependymomas. Also, less than 5% of ependymomas are infiltrative at the time of diagnosis which was not taken into account in the classification of patients. In the other hand biomarkers under study could be good prognosis predictors. One of the most important challenges in the management of intra cranial ependymomas is to determine the most optimal multimodal therapy for these tumours. Surgery has an important role in the treatment of intracranial ependymomas and the extent of resection influence highly the overall prognosis. Nowadays, majority of authors agree to perform surgery on these patients and tend to achieve the most complete resection followed by radiotherapy. In series published by Sutton et al., the survival rate after 5 years was 60% for patients who had a total or subtotal removal against 21% for children who had partial removal or biopsy [11]. However, surgery is rarely curative and recurrences are mainly local.

In our Serie the total resection was achieved in 42.8% of cases (25 cases) with a partial resection in 35.7%. The survival rate after 5 years was 88% after surgery followed by radio therapy. Shu et al. [7] report a survival rate of 40.7-66.2% with a mean survival length of 110.2 months according to a Serie of 49 infants treated at university hospital in Pennsylvania [10]. Mansur, et al. followed up 60 patients in 10 years and had a survival rate of 49.5-55% at Washington university school of medicine with a mean survival length of 12.5 years [12]. Paulino [8] followed up 49 children for 9.6 years and had a survival rate of 60.3-71.4% with 5 years of local control. The conventional radiotherapy has good tumour control after total resection. Radiotherapy should include brainstem and cervical medulla and has less effects on neurocognitive function according to the literature [13-16]. There is no consensus concerning the age to receive radiotherapy, certain authors used radiotherapy in children of 1 year. The benefit of chemotherapy is far from being proved. Some studies suggested that there is no benefit to add chemotherapy concomitant or after radiotherapy. On the other hand, other studies show the efficiency of chemotherapy in anaplastic ependymoma before radiotherapy [17]. Other authors tried to use chemotherapy to delay the need of radiotherapy particularly for vulnerable patients who cannot handle the effect of radiotherapy such as children younger than 3 years old. Ependymomas in children is one of the most frustrating pathologies that the neurosurgeon face from the prognosis point of view. Factors such as age, location, extend of the resection, histological type and the efficiency of complementary treatment are not sufficient to predict the prognosis. Nowadays, molecular biology is interesting for many authors and can identify a group of a poor prognosis with poor global survival. The therapeutic strategy could be then targeted better [18].

Ependymomas are relatively aggressive and resistant to adjuvant therapies. The severity observed during evolution of ependymomas is related to risk of recurrence and CSF metastasis. The total removal of ependymomas is particularly difficult due to their situation inside the ventricular cavity but that remains the best option to achieve a long survival [19-23] (Table 3). In the opposite, the attempt to a total resection exposes the patient to serious morbidity. Adjuvant radiotherapy for patients with a low risk who had complete resection is reasonable option.

Table 3. Survival rate of children after surgical resection followed by radiotherapy according to different series of the literature.

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