With the development of microneurosurgical techniques, the application of various advanced instruments, and intraoperative electrical nerve monitoring (1, 2), the gross total resection (GTR) rate and the postoperative preservation of facial nerve function in vestibular schwannomas (VSs) have significantly improved in recent years. Meanwhile, hearing retention is increasingly becoming the goal of surgical treatment (3, 4). According to previously reported results, in patients with small tumors (<1.5 cm in diameter), 40%–70% have serviceable hearing postoperatively and less than 10% of these have permanent facial weakness (5–7). However, for patients with tumors larger than 2.5 cm in diameter, the rate of serviceable hearing preservation after surgery is less than 5%, and the risk of partial or permanent facial paralysis is about 50% in those with total resection of large tumors (8–10). The complexity of the structure increases with tumor volume, which may cause difficulties for neurosurgeons to identify and protect cranial nerves (CNs) VII/VIII and the brainstem. Surgical techniques based on a better understanding of the membranous characteristics of VSs are necessary for the achievement of satisfactory results.

Sasaki et al. (11) firstly demonstrated the perineurium structure around VSs based on histological observations and introduced the subperineural dissection technique in surgery. Satisfactory resection rates and facial nerve function preservation were achieved in subsequent reports of the application of this technique in VS treatment (12, 13). However, the complicated membranous structure around VSs makes understanding and duplicating the subperineural separation technique difficult. Moreover, there is no report on the effects of the application of this technology in a large series of cases so far. In this study, we applied the subperineural resection technique in the surgical treatment of 124 patients with VSs. We proposed an easily accessible model of membranous structure around VSs and introduced the nuances and pearls of the subperineural technique based on this model in protecting related cranial nerves and the brainstem. Furthermore, we retrospectively analyzed the surgical effects and complications of this technique and presented our experiences.

Conservative treatment, stereotactic radiotherapy, and surgery were employed in the treatment of VSs. For patients with large VSs and obvious clinical symptoms, surgery is still the only option to alleviate the clinical symptoms and cure the tumors (17). The difficulty in obtaining GTR and functional preservation of the facial and auditory nerves increases with the increase of tumor volume.

At present, studies have confirmed that most VSs are subarachnoid, whereas those located outside the arachnoid region occur quite rarely. Kohno et al. (18) confirmed that 86 of 118 patients (73%) were subarachnoid, 2 (2%) cases were extra-arachnoid, and the remaining 30 cases (25%) were relatively large tumors that were difficult to determine. Lescanne et al. (19, 20) also reported that the arachnoid membrane of the CPA cistern continued from the brainstem to the bottom of the internal carotid artery (ICA), and the facial–acoustic nerve complex had no interval and was located under the arachnoid, indicating that the VS was a non-extraarachnoid tumor. It was suggested, by means of optical microscopy and immunohistochemical staining, that the membranous structure covering the tumor surface was arachnoid (18, 21, 22). Ohata et al. (22) further elucidated the rearrangement of the adjacent arachnoid membrane with the tumor growth, which caused different capsule layers of the arachnoid membrane at different sites on VSs, and advocated that the tumor should be dissected and resected along the subarachnoid plane. Furthermore, Sasaki et al. (11) demonstrated that there is a thin layer of connective tissue membrane composed of the perineurium and that some degenerated nerve fibers under it lie on the surface of the tumor. Subsequently, the subperineural VS resection technique was introduced and demonstrated to obtain good surgical results (12, 13). However, it is still difficult to identify the perineurium accurately and to get to the right dissection plane due to the “rearrangement of adjacent arachnoid membrane” out of the perineurium, which may cause this technique to be less repeatable. Based on our surgical experience on 124 VS cases, we combined the “arachnoid membrane rearrangement theory” and the “subperineural resection technique” and proposed a more comprehensive descriptive model of the membranous structure around VSs ( Figures 2A–D ). Better understanding of the membranous structure around VSs based on this model will be greatly helpful for neurosurgeons to identify the accurate subperineural dissecting plane.

In the present study, the subperineural resection technique was demonstrated to effectively reduce the disturbance of the facial–acoustic nerve during operation and to provide an intuitive basis for judging the tumor boundary. It is important to try to avoid breaking through the perineural layer during the entire process of tumor resection. If the perineurium has been accidentally pierced and enters the extra-perineural space as a result, it is necessary to try to reenter the subperineural plane. Esquia-Medina et al. (23) also found that the degree of tumor adhesion, which is mainly evaluated by the nerve displacement, was an important predictive factor associated with facial function. In this study, we proposed a manipulation-based classification in depicting the extent of tumor adhesion to the perineurium and found that older patients and large and cystic tumors were closely associated with severe tumor adhesion, which may significantly affect total tumor removal and nerve function preservation when using this technique. When the tumor has a clear boundary with the perineurium above the brainstem and the facial and cochlear nerves, the tumor could be separated and removed under the perineurium to achieve GTR. However, in the instance of severe adhesion of the tumor to the perineurium (usually at the site near the ICA porus), the function of the facial–acoustic nerve might be damaged if the tumor and the perineurium were detached roughly from the nerves. Therefore, when the interface between the tumor and the perineurium could not be separated using the microdissector, neurosurgeons must use a microscissor to perform sharp dissection in order to create an interface at the mixed level of nerve fibers and tumor cells. In this way, although a small part of the tumor tissue may remain on the perineurium above nerves, the possibility of preserving the function of the facial–auditory nerve will be significantly improved (11, 24, 25).

In addition to the membrane resection technique, which improves the functional preservation of the facial auditory nerve, intraoperative neurophysiological monitoring also plays an important role in anatomical recognition, intraoperative functional preservation, and postoperative prediction (26, 27). Neff et al. (28) pointed out that if the stimulus threshold was ≤0.05 mA or the response amplitude was ≥240 μV, then there is a 98% chance for predicting postoperative facial auditory nerve function as HB grade I or II. Boublata et al. (29) reported on 151 cases of VSs with diameters of 31–60 mm under neurophysiological monitoring and demonstrated that the GTR rate was 82.8%, the anatomical retention rate of facial nerves was 98.7%, and that patients with HB grades of I and II at 2 years postoperatively accounted for 82%. Although the facial–acoustic nerve cannot be seen directly with neurophysiological monitoring, the relative distance between the nerve and the probe can be inferred by adjusting the current required to stimulate the muscle. This suggests that the nerve is highly exposed close to the probe when the evoked potential is obtained with a current of <0.2 mA for stimulation. In contrast, it indicated that a larger tissue or bone barrier existed between the probe and the nerve with stimulation under a current >0.5 mA (30). The retention of auditory nerve function was still not comparable to that of facial nerve function despite the combination of brainstem auditory-evoked potentials (BAEPs), electrocochleograms (ECochGs), and cochlear nerve action potentials (CNAPs) for vestibulocochlear nerve monitoring. More importantly, the larger the tumor, the higher the probability of postoperative hearing loss; for this reason, further clinical research and other electrophysiological monitoring techniques are needed to improve hearing retention (30).

Boublata et al. (29) reported on 126 patients (82.8%) who had GTR tumors, 20 patients (13.9%) who had subtotal tumors, and 124 patients (82%) who had facial nerve function of HB grades I–II 2 years after surgery. The study of Sughrue et al. (31) included 74% of patients who underwent GTR, 11.5% underwent near-total resection, and 14.5% underwent SRT. In a retrospective study of the efficacy of the facial nerve-sparing approach, functional preservation of the facial nerve with HB grade I or II was achieved in 97% after surgery (32). In our group of 124 patients with VSs, the GTR rate was 83.9%, and patients with HB grades I–II postoperatively accounted for 77.4% at 1 week and 88.7% at 6 months. These data indicated that the subperineural technique is effective in obtaining total tumor resection and in preserving facial nerve function.

Although satisfactory results were reported for the resection of total tumor and preservation of facial nerve function, preservation of hearing was still unsatisfactory, especially for large VSs. Zhu et al. (33) reported a postoperative rate of serviceable hearing preservation of 60.9% (67/110) in 110 small VSs (≤1.5cm). Wanibuchi et al. (4) also determined a hearing preservation rate of 53.7% in 592 consecutive patients with VSs (>2 cm in diameter). Surgical tips were introduced as vital to preserving hearing, including bloodless microdissection, subperineural or subcapsular dissection, real-time neurophysiological monitoring, sharp resection of the facial–acoustic nerve, and avoidance of mechanical and heat damage to the brainstem, the nerves, and the internal auditory artery (4, 33). In this study, the hearing preservation rate at 6 months was 43% (15/35). The prognostic factors were analyzed for postoperative hearing preservation, and it indicated that the presence of fundal fluid was a positive prognostic factor. Several documents also stated that the presence of fundal fluid on T2W MRI was predictive of postoperative hearing preservation (33–35). A number of studies confirmed a higher postoperative rate of hearing preservation in tumors originating from the superior vestibular nerve than in those originating from the inferior vestibular nerve, as well as in small tumors than in large tumors (33, 35). However, in our study, we did not find hearing preservation to be related to the tumor origin and size. This may be due to the limited sample of patients with serviceable hearing before operation and most of the recruited patients with preoperative serviceable hearing having large tumors, which may have resulted in poor hearing preservation rate.

The effect of stereotactic radiotherapy in VSs is more and more accepted. For small and medium VSs (≤2.8 cm), gamma knife surgery (GKS) showed good results in terms of tumor control and functional preservation of the facial and acoustic nerves (36). Larger VSs adhere more tightly to the brainstem and facial–acoustic nerve, and the risk of brainstem injury or facial paralysis may be higher after surgery. The treatment strategy combining STR with GKS has been usually selected for larger VSs, also achieving good facial–acoustic nerve functional preservation (32, 37). The classification criterion for the degree of tumor adhesion proposed in this study provides a good reference for neurosurgeons in planning surgical strategy. GTR is relatively easy to achieve in the mild and moderate adhesion group. We strongly recommend that STR combined with postoperative GKS strategy should be adopted when operating on tumors firmly adhered to the perineurium in order to maintain good life quality of patients.

The most serious complications after microsurgery of VSs were intraoperative brainstem injury and postoperative bleeding in the operation area, which were consistent with previous reports (38–40). Bleeding occurred in 5 cases. Of these patients, 1 died due to respiratory and cardiac arrest the next day postoperatively. Craniotomy and hematoma evacuation occurred in 2 cases, and conservative treatment was given in the other 2 cases; eventually, all patients were cured and discharged. Adhesion of the tumor to the brainstem and cerebellum leads to microdamage to the small blood vessels at the junction of tumor and brain tissue, which is the main cause of bleeding (40). Due to the complexity of the surgical procedures, the operation generally lasts longer, especially for larger VSs, and the risks of postoperative fever and intracranial infection could be greater. We carried out procedures such as preoperative lumbar cistern to facilitate intraoperative cerebellar collapse in order to extend the operating space and postoperative continuous drainage of the cerebrospinal fluid until it tested normal in laboratory analysis, which significantly reduced the duration of fever or infection in patients. Another common complication is cerebrospinal fluid otorrhea or incision leakage (5, 41). The incidence of leakage was 3.2% in these cases, which was not very high compared to that in previous literature (40, 41). It is recommended that once mastoid pneumatization is opened, bone wax should be used to seal it tightly, and sometimes it is necessary to cover the muscles on the mastoid for fixation. For the dura mater, a 4–0 absorbable suture was used to close the dural gap, and autologous fascia was responsible for repairing larger dura defects. The procedures were finished by covering the artificial dura, fixing with tissue colloid, and using an elastic bandage for incision compression.

The membranous structure around VSs is complicated and is divergent for each case. The perineurium provides a safe and constant dissecting plane for neurosurgeons to remove the tumor. Fine outcomes have been achieved regarding the GTR rate and the facial–acoustic nerve functional preservation rate with the use of the subperineural technique under neuroelectrophysiological monitoring. The decision to perform radical GTR or STR combined with GKS can be made according to the degree of tumor adherence.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

QY and ZT: chief surgeon, writing—review and editing. WYX, WC, and ZY: writing—original draft preparation. WP, WY, and XYF: data collection and analysis. All authors contributed to the article and approved the submitted version.

This work was supported by the National Natural Science Foundation of China (no. 81971153) and Tangdu Hospital New Technology Plan (nos. XJSXYW2021120, XJSXYW202126).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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