The goal of this case series is to share our experience and results in the treatment of this rather rare entity of spinal cord tumors and compare it to available literature to provide an up-to-date case illustrated review.
The natural history of spinal cord tumors is slowly progressive, and symptomatology usually develops inconspicuously. Given these facts, delay in diagnosis for many months has not been uncommon [9, 26], however widespread availability of MRI and its liberal indication has significantly shortened time to diagnosis . Our data suggest a similar trend with only one patient exceeding more than 3 months of history length. Typical presentation includes motor deficit and pain, as nicely illustrated by presented patients. Acute and dramatic presentation (Patient 2) is rather uncommon for intramedullary tumors and reported only sporadically [8, 36, 39].
Importance of complete tumor removal and factors affecting it
Comprehensive treatment of spinal EP starts with surgery. The goal of surgery should always be GTR; however not at the cost of neurological deterioration. Thus, intraoperative monitoring aiming to maximize safety has become the standard of intramedullary surgery [21, 22]. An overview of case-series reporting outcomes of patients with intramedullary EP separately is given in Table 4. EP are generally more resectable than their more common counterpart astrocytoma, which are more diffusely growing and where a clear tumor to spinal cord margin is often not identified [18, 32]. Nevertheless, a rather wide range of GTR has been reported in the literature, ranging from 25 to 100% [5, 16, 26, 28, 31, 38, 43, 47]. For adults, this number has been more consistently reported between 70 and 100% [6, 14, 18, 22, 44]. Our rate of GTR (40%) falls into the lower part of the spectrum, however, small numbers certainly influence the results. STR was performed in á priori “complicated” patients: a paraplegic patient with a holocord tumor, high-grade EP, and recurrent tumor. The decline of intraoperative monitoring and the decision not to pursue further resection is unsurprising in these patients.
Certain factors such as reoperation , tumor radiation [9, 26, 32], absence of tumor syrinx , tumor grade [2, 3, 26, 37], tumor extent [2, 6], and lower spinal localization [26, 34, 37, 38] have been proposed by some authors as independent factors that may negatively influence the possibility of achieving GTR and thus being prognostic factors for outcome. For example, Oh and colleagues  have proposed that tumor localization may be an independent risk factor for PFS and overall survival (OS). His group has analyzed that a GTR rate of 75.9% was achieved for upper spinal cord EP, whereas only 48.3% for the lower spinal cord EP, which was not explained by other factors such as tumor grade.
Surgical outcome: Postoperative complications and neurological outcome
Numerous studies have consistently reported that a good preoperative neurological status is the single best predictor for good long-term postoperative neurological status [3, 6, 9, 14, 15, 20, 22, 32]. Immediate transient neurological decline after surgery is rather common [2, 32] and related to dorsal myelotomy and surgical manipulation necessary for tumor resection . It is usually completely reversible for most patients in the first 6 months following surgery [2, 18, 32], however, patients and their families should be made aware of its transient nature. In our series, the long-term neurological outcome was favorable with 80% (4/5) patients improving or staying stable neurologically. Unfortunately, severely impaired patients have a very limited chance of neurological improvement; timely diagnosis before significant neurological decline occurs is, therefore, paramount [2, 9, 17].
Spinal deformity is the most reported postoperative complication next to liquorrhea. Both have developed in two of our patients. Literature shows that particularly young children are more susceptible to the development of spinal deformities than adults [9, 30, 32]. It is estimated that around 5–30% of patients will develop spinal deformity, which needs orthopedic intervention [9, 17, 30, 32]. Therefore, in recent years osteoplastic laminotomy is the goal, preferred over complete laminectomy to lower the risk of spinal deformity [17, 26, 30]. Other factors, such as preoperative scoliosis, thoracolumbar localization of the tumor, a younger age, and the number of surgeries are factors, which have been correlated with an increased risk of spinal deformity .
Long-term outcome: Recurrence rate and overall survival
Most studies (ours included) have relatively short follow-ups not reaching adulthood. Lundar et. al.  recently reported the first ultra-long follow-up of children with spinal ependymomas over a span of 8 decades. In their cohort of 33 children (16 grade II/III, 17 myxopapillary), they found relatively good survival rates with 85% and 65% of patients being alive after 10 and 20 years after diagnosis, but they also showed relatively high rates of recurrence rate, particularly among myxopapillary EP. They report cases that presented with recurrence as long as 20 years after the initial surgery supporting the notion that lifelong follow-up is needed in such patients, even after GTR. However, care should be taken to not look at different tumor grades together, as myxopapillary tumors seem to exhibit different biological characteristics and almost exclusively grow extramedullary [1, 27, 43].
GTR, when achieved, usually prevents tumor recurrence and it is the only factor consistently associated in the literature with increased OS and/or PFS [15, 20, 26, 37, 38], in contrast to patients with STR [15, 26, 37, 38]. Our two cases of GTR remained tumor-free in the last-follow up. However, one of them was followed only for one year (the other one for 7,5 years). Following STR, recurrence was observed in our series rather soon; two patients experienced recurrence within the first 6 months and the last patient in 24 months. The fact that two of those three cases were anaplastic EP should be taken into consideration, as they show a more aggressive clinical course . Yet another factor associated with OS is the tumor grade. Safaee et. al.  showed that anaplastic EP were associated with a decreased OS in comparison to lower grade EP, but interestingly not with a decreased PFS. The decreased possibility of achieving GTR in those tumors might be a potential confounding factor, but that hypothesis did not reach statistical significance in their analysis [26, 37]. The question remains, whether age and gender are prognostic factors for OS and/or PFS. While some authors found a positive association of female gender with outcome , others did not [5, 37]. A similar situation exists with the effect of age [5, 24, 37].
The current role of radio- and chemotherapy
Current clinical practice is imperfect and orientates itself on studies performed on intracranial EP and/or adult EP patients [4, 26]. Good long-term results have been reported repeatedly for children in which GTR has been achieved without radiotherapy for grade II EP and therefore currently not recommended [4, 17, 26, 38]. STR with RT has been shown in some studies in adults to be superior to STR alone but remains a topic of controversy [6, 25, 33, 44]. Any potential benefit must be juxtaposed to potential damage conferred onto the developing osseous and nervous system in this age group [20, 30, 48]. In practice, radiotherapy is usually reserved for cases of anaplastic EP or inoperable tumors, even though there is a lack of data proving efficacy for both adults and children due to the small number of cases [4, 6, 44]. Despite the good response encountered in one of our patients to chemotherapy, the role of chemotherapy itself in the treatment of intramedullary EP is unclear. Chemotherapy if used is usually for cases of recurring and/or anaplastic EP as a way of improving the prognosis by all means possible [7, 12, 42]. However, the evidence is poor, due to the small number of patients and the heterogenicity of applied regimens reported in the literature [4, 44]. Larger patient cohorts will be ultimately needed to evaluate the potential benefit of chemotherapy regimens designed for intracranial EP for spinal EP, such as seemingly encountered in one of our patients .
The main limiting factor, along with other publications [5, 16, 26, 28, 31, 38, 43, 47] reporting on childhood spinal cord EP, is the small number of patients enrolled in this study alongside the usual shortcomings of a retrospective study design. The incidence of one EP patient every 3–4 years falls in line with other single-institution series [9, 28, 38]. Therefore, our data remains descriptive, as statistical analysis of such a small cohort is not feasible. Although our treatment and follow-up protocol remained consistent during the study period, important clinical data could have been missed.