Facial nerve elongation as predictive factors of facial nerve outcome after the vestibular schwannoma resection

Background: To analyze risk factors affecting the long-term facial nerve functional outcomes in patients receiving vestibular schwannoma surgery. Method: A total of 89 cases receiving vestibular schwannoma surgery via retrosigmoid sinus approach were analyzed retrospectively. The facial nerve functional outcomes of all enrolled patients were evaluated 6 months after the operation according to House-Brackmann grading scale. The relationships between facial nerve injury and its potential risk factors were analyzed. Results: Postoperative facial nerve injury was found in 53 patients (59.6%) 6 months after the operation. The results of univariate logistic regression analysis indicated that the tumor volume, the maximum tumor diameter, the facial nerve elongation, the enlargement of internal auditory canal (IAC), the IAC size on the affected side, and the facial nerve adhesion to tumor were signicantly correlated with the occurrence of facial nerve injury. The multivariate logistic regression analysis revealed that the facial nerve elongation, the facial nerve adhesion to tumor, the tumor volume, and the enlargement of IAC were the independent risk factors of facial nerve injury 6 months after vestibular schwannoma surgery. The ROC curve showed that the cut-off points of the facial nerve elongation, tumor volume and enlargement of IAC were 2.925cm,10.965 cm³ and 1.818 respectively. When the cut-off points were exceeded, the possibility of facial nerve injury would largely increase. Conclusion: With the growth of the facial nerve elongation, the tumor volume, the facial nerve adhesion to tumor, and the enlargement of IAC, the possibility of facial nerve injury after the vestibular schwannoma surgery would accordingly increase.


Background
Vestibular schwannoma (VS) is a benign intracranial tumor growing in the internal auditory canal (IAC) and the cerebellopontine angle. It easily compresses the peripheral nerve leading to tinnitus, hearing loss, and facial paralysis. The surgical procedure is the main mode of treatment for VS. Facial nerve injury is one of the most serious postoperative complications of VS, which brings about paralytic eyelids and dis guring facial palsy. Previous studies have con rmed that postoperative facial nerve injury signi cantly decreases the quality of life in VS patients [1,2]. Therefore, identifying risk factors for postoperative facial nerve injury is extremely urgent to help to improve facial nerve function after VS resection.
Accumulated studies have recognized the tumor size as an independent risk factor for postoperative facial nerve injury [3][4][5][6][7][8]. However, discrepancy on the other associated risk factors still exists, for example, the facial nerve adhesion to tumor and facial nerve location. Through evaluating published researches, we can carry out further research on the basis of previous research. For instance, Walz, et al calculated tumor size using the maximum tumor diameter, which was not consistent with the actual tumor size [9].
Due to the difference in the internal auditory canal (IAC) size among individuals, it is di cult to demarcate the enlargement of IAC. Also, the degree of tumor compression to the facial nerve was not included adequately in the research analysis. Moreover, although the size is important, also important is the location of epicenter of the tumor, thus some discrepancies in some of the studies in the literature.
Compared to other studies, this study innovative introduced the concept of the facial nerve elongation to measure the location of epicenter of the tumor.
In order to solve these problems, we conducted this study to explore accurate associations of the potential risk factors including the facial nerve elongation, the enlargement of IAC, and the tumor volume with the postoperative long-term facial nerve function.

Object
A total of 89 VS patients treated in the Neurosurgery Department from January 2010 to December 2020 were analyzed retrospectively. Vestibular schwannoma surgery via retrosigmoid sinus approach was conducted in all patients. The electrophysiological technique was used to monitor the facial nerve function intraoperatively. The exclusion criteria were as follows: preoperative facial nerve injury, the unprotected facial nerve in operation, residual VS found in postoperative follow up recurrent VS.

Clinical data
Patients' gender, age, preoperative duration of symptoms (time from the initial onset of clinical symptoms to the surgery), duration of operation, intraoperative bleeding volume, and postoperative pathological results were collected through the electronic medical record system ( Table 1).
The radiologic parameters of enrolled patients were collected by craniocerebral MRI and/or CT, including maximum tumor diameter (the maximum diameter of the tumor outside the IAC measured by T1weighted MRI, Figure 1), side of tumor (left or right), tumor properties, IAC enlargement or not (>6mm was recognized as enlarged), maximum IAC diameter on the affected side and normal side, facial nerve elongation , tumor volume, and tumor grade (KOOS grade) ( Table 1).
VS was divided into cystic (non-enhanced MRI), solid-cystic (heterogeneous enhanced MRI), and solid (homogeneous enhanced MRI) VS according to the tumor properties [10].
Three-dimensional reconstruction of the tumor was performed using Mimics19.0 software to obtain the tumor volume data ( Figure 2). As shown in Figure 3, The maximum IAC diameters on the affected side and normal side were measured. The enlarged degree of the IAC was de ned as the ratio of the maximum IAC diameter on the affected side to the maximum IAC diameter on the normal side.
The deformation of facial nerve compressed by the tumor was frequently observed in vestibular schwannoma surgery. However, the compressional deformation degree of facial nerve has rarely been analyzed. In this study, the facial nerve elongation was introduced to evaluate the compressional deformation degree based on the axial MRI or coronal MRI ( Figure 4). The facial nerve elongation was de ned as the length of the tumor edge from the opening of IAC to the intersection of the facial nerve (long axis) with the brainstem.
The degree of facial nerve adhesion to tumor was determined and recorded by the chief surgeon during the operation. Facial nerve adhesion to tumor could be divided into three degrees, including no adhesion (the anatomical structure between the tumor and the facial nerve is clearly visible and easily separated), mild adhesion (the anatomical structure between the tumor and the facial nerve can be distinguished and separated with a few di culties), and severe adhesion (the anatomical structure between the tumor and the facial nerve is unrecognizable and hard to be separated).
The positions of facial nerve relative to the tumor (anterior type, posterior type, superior type, and inferior type) were evaluated and recorded by the chief surgeon during the operation.

Evaluation of facial nerve outcomes
The facial nerve functions of all patients were evaluated preoperatively and 6 months after the operation. According to the House-Brackmann scale, the postoperative facial nerve functional outcomes of grade 1 and grade 2 were de ned as normal, while grade 3 to 6 were de ned as facial nerve injury.

Statistical analysis
SPSS version 23.0 was used for statistical analysis. Qualitative data were represented by the number of cases (percentage) while quantitative data were represented by the average ± standard deviation (maximum-minimum). The correlation between potential risk factors and facial nerve injury 6 months postoperatively was statistically analyzed by binary univariate logistic regression analysis. The signi cant risk factors in univariate analysis were then included in multivariate logistic regression analysis by using the forward stepwise regression method based on maximum likelihood estimation. A signi cant difference was achieved when p < 0.05. The R Studio 3.6.3 and the pROC packages were used to draw the ROC graph.

Discussion
A variety of therapeutic approaches including follow-up observations, surgical treatments, and stereotactic radiotherapy could be recommended for VS patients. Vestibular schwannoma surgery is the rst choice for symptomatic patients. Although the microsurgical and imaging technology have made much progress in recent years, the postoperative facial nerve injury in patients receiving vestibular schwannoma surgery is still inevitable, which greatly reduces the quality of life [1,2]. To intraoperatively improve the protection of facial nerve, we identi ed the factors that might affect the long-term facial nerve function of patients receiving vestibular schwannoma surgery.
During the surgery, we found that due to the difference growth pattern and locations of epicenter of the tumor, the facial nerve location and deformation degree were differences. Despite some tumors volume were small, but due to their growth direction facing the face nerve which could cause severe pushing of the facial nerve, and some tumors were large, but their growth direction is opposite to the facial nerve, which makes the facial nerve receive lighter pushing. Therefore, this study innovative used the concept of the facial nerve elongation in order to explore the relationship between the facial nerve deformation degree and post-operative facial nerve function. The results of logistic regression analysis showed that facial nerve elongation was an independent risk factor and positively correlated to facial nerve injury 6 months after operation, whichresults were not founded in the past . Besides, the ROC curve analysis showed that the possibility of facial nerve injury increases largely when the facial nerve elongation is larger than 2.925cm.
The fact that tumor size affects the postoperative facial nerve functional outcomes has been widely recognized [6,14,15]. Most of previous studies evaluated the tumor size by calculating the maximum tumor diameter. However, a big deviation exists when the maximum diameter is used to represent the actual tumor size [9]. Here, we used the tumor volume to measure the tumor size. The results of logistic regression analysis showed that tumor volume was an independent risk factor and positively correlated to facial nerve injury 6 months after operation, which is consistent with published studies [4,16]. Besides, the ROC curve analysis showed that the possibility of facial nerve injury increases largely when the tumor volume is larger than 10.965cm³.
The relationship between the enlargement of IAC and the postoperative facial nerve injury remains controversial [4,17]. In previous study, the IAC was mostly divided into enlarged or not even though the IAC sizes in patients differ greatly. Distinguishing whether the IAC enlarges or not according to one standard is not suitable. In this study, the enlarged degree of IAC was used to evaluate IAC size to reduce the potential error. The results showed that the possibility of long-term postoperative facial nerve injury increased as the enlarged degree of IAC grew. When enlarged degree of IAC exceeded the cut-off point of 1.88, the risk of facial nerve injury 6 months after the operation would largely increase.
The compressional deformation of facial nerve has rarely been included as a risk factor to be analyzed in previous studies. In clinical practice, we found that the postoperative facial nerve injury was prone to appear when the facial nerve was compressed and deformed seriously. Thus, the facial nerve elongation was introduced and statistically analyzed in this study. The univariate logistic regression analysis showed that the facial nerve elongation was signi cantly correlated with facial nerve injury after vestibular schwannoma surgery, while multivariate logistic regression analysis revealed that facial nerve elongation was not an independent risk factor for facial nerve injury. These suggest that facial nerve elongation could be used as a potential predictive factor for postoperative facial nerve injury in patients receiving vestibular schwannoma surgery. However, the distributional course of facial nerve was not limited to the aforementioned four types. Using the MRI to evaluate the facial nerve elongation was not precise, which lead to potential error. Diffusion tensor image-based three-dimensional reconstruction could be used to reconstruct the distribution of facial nerve [18][19][20] and to accurately evaluate the facial nerve elongation in the future.
In addition, this study showed that the facial nerve adhesion to tumor was an independent risk factor for facial nerve injury, which was consistent with the ndings of Renato Torres et al. [3,21]and with the clinical experience of surgeons.There are still some defects in this study. First, the number of patients enrolled in this study is not su cient to get a precise conclusion. Second, several potential confounding risk factor, such as the blood pressure, blood glucose and so on, are not included to be analyzed.

Conclusion
In summary, with the growth of the facial nerve elongation, the tumor volume, the facial nerve adhesion to tumor, and the enlargement of IAC, the possibility of facial nerve injury after the vestibular schwannoma surgery would accordingly increase. Consent for publication: Written informed consent for publication was obtained from all participants.
Availability of data and material: The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.
Competing interests: No competing interests exits in the submission of this manuscript.

Funding : Not applicable
Authors' contributions: Zhi Zhu and Ningning Song analyzed and interpreted the patient data, and were major contributors in writing the manuscript. Weichao Jiang, Xi Chen, Sifang Chen recorded and collected patients' information, and also participated in writing the manuscript. Guowei Tan performed surgeries for most of cases and designed this study. All authors read and approved the nal manuscript.