Prophylaxis with nimodipine and dexamethasone as prevention of delayed facial nerve lesion following vestibular schwannoma resection

Summary

Aim: This study aimed to evaluate the effect of nimodipine in combination with dexamethasone on the incidence of delayed facial nerve palsy after vestibular schwannoma resection. Materials and methods: A retrospective analysis was conducted on a group of patients who underwent vestibular schwannoma resection between 2002 and 2016, when neither nimodipine nor dexamethasone were used as standard therapy and then compared with patients treated between 2016 and 2023, after pharmacoprophylaxis with these agents had been adopted as routine practice during surgery for vestibular schwannoma. Delayed facial nerve palsy was defined as a deterioration of two or more grades in the House-Brackmann scale compared with the early postoperative status, occurring between the 5^th (inclusive) and the 30^th postoperative day. Results: A total of 111 patients who underwent vestibular schwannoma resection were included in the analysis, comprising 49 patients who received pharmacoprophylaxis and 62 patients who did not. Delayed facial nerve palsy developed in eight patients (7.2%), with two cases (4.1%) in the pharmacoprophylaxis group and six cases (9.7%) in the non-treatment group (P = 0.226). Conclusion: The descriptive findings of this study suggest a potentially favorable effect of prophylactic administration of nimodipine and dexamethasone in reducing the risk of delayed facial nerve palsy after vestibular schwannoma resection.

Keywords:

Facial nerve – vestibular schwannoma – dexamethasone – facial palsy – facial nerve injury – nimodipin

This is an unauthorised machine translation into English made using the DeepL Translate Pro translator. The editors do not guarantee that the content of the article corresponds fully to the original language version.

Introduction

Late facial nerve damage occurring after vestibular schwannoma resection is a relatively common complication with an incidence of 13–41% [1]. For patients, this represents a significant occupational, social, and psychological limitation, particularly because it often develops in a functionally sound nerve only after discharge from the hospital to the home environment. There is general consensus in the medical literature that late facial nerve dysfunction is a deterioration in facial nerve function following vestibular schwannoma surgery compared to the immediate postoperative state. Individual definitions vary in their time criteria, which most commonly range from 48 hours to 30 days after surgery. Another variable is the severity of the deterioration on the House-Brackmann (HB) scale—some authors require a deterioration of at least two grades, while others require only one. For these reasons, there is a wide range in the reported incidence [1–3].

The pathophysiology has not yet been conclusively elucidated. Some studies suggest that nerve damage during surgery, followed by axonal degeneration, is responsible for the earlier onset of late lesions (≤ 48 hours); this type is also associated with a longer recovery period [3]. Other studies propose a hypothesis involving spasm of small perineural vessels or swelling of the facial nerve within the canalis nervi facialis, leading to the development of compressive ischemia [4,5], which is associated with demyelination [3]. Completely separate from these is the theory of reactivation of the herpes simplex or varicella zoster virus, which may be associated with an increase in the titer of antibodies against these viral agents in the serum [6].

If a late-onset facial nerve lesion develops, efforts are made to minimize the consequences and shorten the recovery period; however, the prognosis is very good even without pharmacotherapy. Most patients recover completely or achieve very good nerve function (HB I or II) [2]. Frequently administered anti-edema therapy or a combination of anti-edema and antiviral drug therapy has not been shown to shorten the recovery period or improve nerve function [2].

In our study, we monitored the incidence of late lesions in two groups of patients: one group received prophylactic therapy with a combination of nimodipine and dexamethasone, while the other group received no pharmacological prophylaxis.

The aim of our study was to evaluate the preventive effect of vasoactive therapy on the development of late facial nerve lesions following vestibular schwannoma resection.

 

Methodology

This study involves a retrospective evaluation of patients who underwent vestibular schwannoma resection between 2002 and 2023. We defined late facial nerve damage as a deterioration in the function of the seventh cranial nerve by at least two or more grades on the HB scale compared to the early postoperative status, occurring between the 5th postoperative day (inclusive) and the 30th day after surgery. Consequently, only patients who, in the period immediately following surgery through the 5th postoperative day, had facial nerve impairment of no worse than grade 4 on the HB scale [2] were included. Patients in whom the vestibular schwannoma was part of a genetically determined disease (type II neurofibromatosis) or who died within 2 years of surgery were excluded.

Patients were divided into two groups. The first group underwent surgery between 2002 and 2015. The second group underwent surgery in 2016 or later, when our center began routinely administering vasoactive therapy to all patients indicated for vestibular schwannoma resection. This pharmacoprophylaxis was administered as part of a standardized perioperative protocol with the aim of reducing the risk of damage to the facial nerve and cochlear nerve. We evaluated a total of 111 patients. The group receiving vasoactive therapy consisted of 49 patients; the remaining 62 patients received no prophylaxis.

The status of the lesion was continuously assessed during hospitalization, at discharge, and subsequently during regular outpatient follow-up visits at 6 weeks, 6 months, and 1 year after surgery. The severity of the lesion was assessed using the HB scale.

The resection was performed via a retrosigmoid craniotomy. Facial nerve function was monitored during the operation using electrical stimulation (Neurosign 100, Magstim. Comp. Ltd, Whitland, United Kingdom). When the goal was to preserve hearing, cochlear nerve function was monitored using brainstem auditory evoked potentials (BAEP) (Eclipse, Medtronic, Dublin, Ireland).

The data were analyzed with an emphasis on the descriptive nature of the study and the limited number of observed events.

Fisher’s exact test was used to compare categorical variables between groups. For continuous variables, nonparametric comparison using the Mann-Whitney U test was preferred in cases of non-normal distribution or a small sample size; when the distribution was approximately normal, the unpaired Student’s t-test could be used.

The primary outcome measure was the incidence of late facial nerve lesions. In addition to the p-value, effect size measures were also calculated for the primary outcome, specifically the absolute risk difference, relative risk, and odds ratio (OR), each with a 95% confidence interval (CI) (R Core Team, Vienna, Austria).

Given the very low number of events (a total of 8 cases of late facial nerve palsy), multivariate regression analysis was not performed, as its results would have been statistically unstable and difficult to interpret. The results should therefore be considered primarily exploratory and hypothesis-generating.

The level of statistical significance was set at p < 0.05. All tests were two-sided.

 

Protocol

Nimodipine was administered orally the day before surgery at a dose of 2 tablets 6 times a day (Nimotop S 30 mg tablets, Bayer, Leverkusen, Germany); during surgery, it was administered intravenously (Dilceren 0.2 mg/mL, Zentiva, Prague, Czech Republic) continuously at a rate of 1 mg per hour; and subsequently, for seven days after surgery, 2 tablets 6 times a day by mouth (Nimotop 30 mg tablets). Dexamethasone (Dexamed 4 mg tablets, Medochemie, Limassol, Cyprus) was administered intravenously prior to surgery, intravenously 4 mg four times daily on the day of surgery, and subsequently orally at a tapering dose until the 7th postoperative day.

 

Results

The mean age of patients in the study cohort was 53.5 years at the time of surgery; women slightly outnumbered men (59/52). The mean size of the vestibular schwannoma was 24.9 mm, and the mean score on the Koos scale was 3.1 (Table 1).

A total of eight patients (7.2%) out of the 111 studied developed late facial nerve damage, including six of the 62 patients in the group without pharmacoprophylaxis (9.7%; 95% CI 3.6–19.9%) and two of the 49 patients in the group receiving pharmacoprophylaxis (4.1%; 95% CI 0.5–13.9%) (Fig. 1). The difference between the groups was not statistically significant (Fisher’s exact test, p = 0.226). The relative risk with pharmacoprophylaxis was 0.42 (95% CI 0.09–2.00) and the odds ratio (OR) was 0.40 (95% CI 0.08–2.06).

Of the eight patients who developed a late lesion, seven recovered completely or to mild facial nerve dysfunction (HB I or II) (including both HB I cases in the group receiving vasoactive therapy); one patient in the group without vasoactive therapy continued to have a Grade III lesion.

All patients who developed a lesion had a fully functional facial nerve (HB I) prior to surgery; in all patients, the continuity of the facial nerve was preserved perioperatively, and perioperative electrophysiological stimulation was elicitable (in seven patients at 0.5 mA, in one patient at 2.0 mA).

The baseline postoperative grade according to the HB scale in the group without therapy was II in four patients and III in two patients (mean 2.33); following the development of a late lesion, the grade worsened to III in one patient, to IV in two patients, and to V in three patients (mean 4.3). In the group receiving vasoactive therapy, the baseline grade was I and II (mean 1.5), and the lesion worsened by two grades in each case (HB III and HB IV; mean HB after worsening 3.5) (Fig. 2).

Among patients in whom the lesion progressed, the average age was 45.9 years, and women outnumbered men three to one (6 : 2). Tumor size ranged from 12 to 47 mm in its largest dimension, and on the Koose scale, vestibular schwannomas were most commonly grade IV (5), followed by grade III (2) and grade II (1). Fig. 3 and Table 2 summarize the distribution of these values in both groups.

In our cohort, we did not observe any serious adverse effects of the administered medications that would have necessitated discontinuation of treatment. In particular, symptomatic arterial hypotension requiring vasopressor support was not recorded.

 

Discussion

Nimodipine is a calcium channel blocker that is often cited as an effective protective agent for preserving the auditory and facial nerves following vestibular schwannoma surgery [7–9]. Its neuroprotective effect acts on several levels—at the vascular level, it primarily dilates cerebral blood vessels [10]; at the cellular level, it activates the transcription of neurotrophic factors, calcium-binding proteins, and antioxidants [11]; and it significantly reduces cell death caused by osmotic, oxidative, and thermal stress in astrocytes, Schwann cells, and neurons by inhibiting caspase-induced apoptosis [11,12]. At the neurochemical level, it promotes neurite outgrowth and axonal remyelination [13] and reduces the levels of pro-inflammatory cytokines [14]. Dexamethasone, on the other hand, is a long-acting corticosteroid with a pronounced anti-edematous effect [15].

In our study, we followed the protocol used by Scheller et al. in their paper, in which they compared the oral and intravenous forms of nimodipine [16]. Pharmacoprophylaxis is modeled after the enteral group, with the exception of intraoperative administration; at our center, nimodipine is administered intravenously to avoid the need for a nasogastric tube.

For the purposes of this study, we adopted the definition of a late lesion according to Carlstrom et al. [2], which defines the onset of a late facial nerve lesion as occurring between the 5th (inclusive) and 30th postoperative day. The choice of the 5th postoperative day as the cutoff is based on the assumption of distinct pathophysiological mechanisms underlying early and late lesions. While a later onset is more frequently associated with vasospasm or nerve edema, an early-onset lesion (< 48 h postoperatively) is, according to some studies, more closely associated with nerve injury during surgery and subsequent axonal degeneration [3].

If we were to define late-onset facial nerve palsy as any deterioration in facial nerve function following the initial postoperative assessment [1], the overall incidence would increase to 14.1%, and the incidence in both groups would nearly double (9.3% in the group receiving vasoactive therapy, and 17.7% in the group without vasoactive therapy). Based on this, it can be surmised that pathophysiological mechanisms other than just nerve damage during surgery may also be responsible for the early onset of late lesions [3].

Although we observed a decrease in incidence in the group of patients who received vasoactive therapy, our results did not reach statistical significance. The main limitation of the study is its retrospective nature and the comparison of two cohorts from different time periods, which may be subject to differences in surgical technique, perioperative care, and surgeon experience. Another significant factor is the heterogeneity of the groups in terms of tumor size (21.7 vs. 28.0 mm), which may influence the incidence of the complication under study, as well as the small number of surgeons.

To verify our hypothesis, it would be appropriate to conduct research on a larger number of patients.

At the same time, it should be noted that the administration of nimodipine for this indication constitutes off-label use; however, this is supported by available experimental and clinical studies suggesting its neuroprotective effect on the cranial nerves [8,9,15,16].

 

Conclusion

In our cohort, there was a decrease in the incidence of late facial nerve lesions following vestibular schwannoma resection in the group receiving vasoactive therapy compared with the group without vasoactive therapy. At the same time, the functional outcome one year after surgery was better in patients with nerve lesions in the group receiving prophylactic administration of nimodipine and dexamethasone. However, due to the small number of subjects, the result was not statistically significant. Nevertheless, the descriptive results of our study suggest a positive effect of vasoactive therapy in reducing the risk of developing late facial nerve lesions following vestibular schwannoma resection.

Based on these findings, we plan to continue implementing this protocol in patients indicated for vestibular schwannoma resection, not only because the incidence of late lesions was more than twice as low in the prophylaxis group, but also because of its positive effect on preserving cochlear and facial nerve function following vestibular schwannoma surgery [8,9].

 

Ethical Considerations

The authors declare that the patient’s surgery was performed after he had been informed in accordance with the ethical standards of the Ethics Committee of Masaryk Hospital, which is responsible for conducting clinical trials, and the 1974 Declaration of Helsinki, as revised in 2000. The study was approved by the Ethics Committee of Krajská zdravotní a. s., Masaryk Hospital in Ústí nad Labem o.z. on January 21, 2026, reference number: 343/7.

 

Conflict of Interest

The authors declare that they have no conflict of interest in connection with the subject of the study.

 

 

 Table 1. Summary of the basic characteristics of patients who underwent vestibular schwannoma resection between 2002 and 2023.

	Group receiving vasoactive therapy	Group without vasoactive therapy
Sex (F/M)	29/25	30/27
Average age at the time of surgery	52.3 years	54.6 years
Average VS size at its largest dimension (mm)	21.7 mm	28.0 mm
Average grade according to Koos	2.9	3.2

M –⁠ men; VS –⁠ vestibular schwannoma; W –⁠ women

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

	Sex (F/M)	Average age at the time of surgery	Average grade according to Koos	Average VS size at its largest dimension (mm)
Group without pharmacoprophylaxis	5/1	47.0 years	3.7	28.2
Group with pharmacoprophylaxis	1/1	42.5 years	3.0	21.0

 

 

Table 2. Summary of basic characteristics of patients who developed late paresis following vestibular schwannoma resection.

 

M –⁠ men; VS –⁠ vestibular schwannoma; F –⁠ women