The kinetics of postoperative recovery of CN disorders is an original aspect of this work, which demonstrates the favorable effect of surgery on the functional outcome of CN function, with a low rate of long-term morbidity since postoperative CN deficits were mostly transient.
This study is one of the largest surgical series of CPA-PCA EC published so far, with a total of 56 patients. The literature dealing with the same topic is scarce and only a few retrospective cohort studies include more than 30 patients.[5, 7, 12, 13, 19, 23, 24]
CN preoperative deficit
We report here the very good evolution of preoperative CN disorders after surgery, with an improvement of 72% of preexisting deficits, regardless of the approach or the location (PCA or CPA) of the cyst.
Both the inflammatory effect induced by the cystic content and the direct mechanical compression over the cisternal segment of the CN by the tumor, may explain preoperative CN disorders favorable outcome after surgery, even with small volume cysts. Contrary to schwannoma or meningioma cases wherein the CN are shift by the boundaries of the tumor capsule, EC invade the cisternal space by adapting their shape to the local morphology, encompassing nerves and vessels. Thus, surgery might improve symptoms by reducing cystic content and inflammatory process over the nerve in addition to reducing the mass effect. In this way, GTR has a greater impact than STR and PR on the improvement of pre-operative CN deficits in our series (88% of improvement VS 53% and 69%, p=0.196): maximal resection of cystic content and capsule fragments results in a higher reduction of local irritation. The effects of local irritation by the cholesterol seeping through the cyst wall have already been reported in previous study, in cases of hyperactive dysfunction such as trigeminal neuralgia or hemifacial spasm. [5, 9] Vascular compression of the nerve, either by a displaced artery or by nerve displacement toward the artery by the tumor has also been relieved.[5, 13]
The beneficial effects of surgery on these preoperative CN deficits had also been demonstrated in several series. Of the 17 CPA EC reported by Czernicky et al, 11 patients experienced improvement or resolution of their preoperative deficits, in particular with trigeminal neuralgia, LCN deficits and facial nerve deficits. In their cohort of 37 EC patients, Gopalakrishnan et al demonstrated a significant improvement in trigeminal and lower cranial nerve dysfunction after surgery, and half of the CN VIII and oculomotor deficits . Of the 21 patients with preoperative CN dysfunction reviewed by Schiefer and Link, 33% were resolved (n = 7) after the surgery and 43% were improved (n = 9). In Vernon et al series of 139 patients, 74% of them improved compared with their preoperative clinical status. Prior to our series, none of these studies attempted to analyze the association between these CN improvements and surgical approach or EOR. Of note, none of them included PCA location of the cyst, and the TP approach was not used.
Postoperative new CN deficit
New CN deficits occurred during the immediate postoperative course in almost 50% of our patients. Most of them, apart from cochlear impairment, tended to resolve during the follow-up period. The unique cisternal cytoarchitecture of the VIII CN (i.e. centrally myelinated) could explain its higher surgical vulnerability in comparison to the other CN. Moreover, postoperative CN VIII impairment is related to direct nerve dissection or vasculature damage during surgery because of the adhesion between the lesion and the nerve and is therefore less likely to recover.
TP approach tended to increase postoperative impairment, especially oculomotor deficits (p = 0.001). However, most of them were transient and TP approach remains advantageous for some PCA locations, particularly when the cyst crosses the midline or straddles the basilar artery. Thus, this approach must remain systematically considered to ensure the best surgical exposure.
The high rate of postoperative CN injury, resulting from the adhesion of the tumor capsule to the nerve, is a well-known complication of this surgery. Very few studies have detailed the evolution of CN deficit over time.[4, 5, 7, 12, 13, 20, 23]. Vernon et al reported 41% of new postoperative deficits, which resolved completely on long-term follow-up in 21% patients, improved significantly in 10% patients, and remained at an unchanged level in 9% patients. Czernicki et al provided comparable results in term of frequency and evolution of CN deficit, with 58% of new postoperative CN injury (n = 10) and persistent cochlear deficits during follow-up. Similar to our series, the EOR had no effect on the occurrence of new postoperative deficits. In Gopalakrishnan series of CPA EC, only 13% (n = 5) of the 38 new postoperative deficits persisted at long term follow-up. They reported a higher incidence of new neurological deficits in patients undergoing total removal compared to subtotal removal, but at the same time, the former group experienced a better improvement in preoperative neurological deficits compared to the latter one. Two series have reported a lower rate of postoperative deficit.[5, 12] The cohort of 30 patients undergoing retrosigmoid surgery associated with whole course neuroendoscopy of Hu et al experienced only 7% of new deficits. Finally, two papers have reported a higher rate of new postoperative deficit, but with a very good improvement over time.[13, 20] Despite these differences in term of postoperative CN deficit, our cohort covered a larger group of accurately and sequentially monitored patients than previously reported, which was the main objective of this work, and strengthen our findings.
Long term general condition was good to excellent for most of patients. Only 2 patients presented a WHO PS score at 3 or 4 (capable of limited self-care or completely disabled) at the end of follow-up. In the literature, two other series have recorded long-term general condition, and their results were similar.[4, 20] Eighty-eight percent of patients were able to carry out all usual activities (modified Rankin score of 0 or 1) in Czernicki‘s cohort, and 84% for Schiefer’s cohort. These results are linked to a cautious surgical strategy, avoiding maximalist resection of the fragments adhering to the brain stem, vessels or nerves. The fact that EC are mostly managed in young and healthy patients favorably outweigh the outcome.
Tumor control and onco-functional balance
Twenty-six patients (46 %) showed evidence of tumor progression during the follow-up period, after a median duration of 63 months. The factors that might predict a stable behavior instead of a keep growing ones couldn’t be unveiled by our study. Based on our experience, patients with postoperative residual lesions had no increased risk of progression or recurrence during follow-up (p = 0.394). This result could be due to many biases inherent to the design of the study, and to the short follow-up of only 46 months. In our work, GTR rate (14%) is lower and recurrence rate (46%) higher than those previously reported for posterior fossa EC: Farhoud et al (32 patients, 59% GTR rate, 0 recurrence), Samii et al (40 patients, 75% GTR rate, 8% recurrence rate), Kobata et al (30 patients, 57% GTR rate, 7% recurrence rate), Vernon et al (139 patients, 73% GTR rate, 8 % recurrence rate), Yawn et al (47 patients, 46% GTR rate, 8% recurrence rate) or Schiefer et al (24 patients, 54% GTR rate, 25% recurrence rate) for instance.[5, 13, 19, 20, 23, 24] Recurrence rate in Gopalakrishnan et al series was higher after long term follow up : 45% of patients showed evidence of tumor recurrence after a mean duration of 9.3 year. Indeed, our definitions of GTR and recurrence were strict, and non-total resections and recurrence rate could have been overestimated.
Postoperative tumor control results are heterogeneous in the literature. Like our study, some reports found no difference in tumor progression after complete or incomplete resection, even after longer follow-up periods (respectively 11,5 years and 4,3 years of follow up).[13, 20] In contrast, some authors found a higher rate of recurrence after non-total resection [7, 19, 22]. A recent large meta-analysis including 691 patients with intracranial epidermoid tumors found that STR was associated with a 7-times higher rate of regrowth than tumors that underwent GTR. However, the analyses were not stratified according to the intracranial location of the cysts, such as infratentorial sites. Moreover, capsule adherence to the neurovascular structures in PCA and CPA locations makes total removal extremely challenging. Additionally, the propensity of EC for regional spreading toward neighbor cisterns hampers the ability to expose the full volume of the cyst “behind the corner” using regular approaches. The use of angled endoscopes (endoscopic assisted microsurgery) could be of help to check for fragments that could be overlooked under microscope, as suggested above.[10, 12]
These findings confirm that altogether, operative findings and high field MR doesn’t reach the level of sensibility to insure the cure of the disease. EC grow linearly, not exponentially, and the overlooked micro-fragments of cyst walls have the propensity to regrowth which is empirically known.[4, 5, 9, 12, 14, 20, 21]
Our results (see Kaplan Meier plot, Figure 5A) underline that recurrence or regrowth might be expected in the ultra-late period, regardless the EOR of the cyst. Patients should be aware and a clinic-radiological sequential follow-up must be planned in long term. Only half of the growing residual tumors justified additional surgery (see Kaplan Meier plot, Figure 5B). The expectation for clinical symptomatology in 85% of reoperated patients can explain the half-year delay before considering surgery.
This is a retrospective study, and so there may be missing data in our work. Also, the center effect has not been tested. Multivariate analysis and cox-regression analysis was not performed, because not appropriate to this limited patient sample. We deliberately merged the findings of PCA and CPA EC in our work; these locations are not supposed to carry the same risks when surgically approached. However, testing this variable did not impact the functional nor the oncological results.
Finally, it would have been interesting to obtain precise volumes and growth rates of the preoperative and residual EC. DWI sequence is essential for the diagnosis of EC and differentiation from other lesions, as the content of the epidermoid cysts shows prominent diffusion restriction due to layered microstructure of the debris . However, this sequence is mediocre in term of anatomical resolution, and did not allow precise calculation of cyst size. The interest of new sequences coupled to the DWI in order to increase the three-dimensional resolution while keeping an important sensitivity and specificity for the diagnosis of EC is an axis to develop in the future.
Last, the length of follow-up did not reach the long-term which weaken the analysis of tumor growth potential over time.