Prophylactic nimodipine treatment improves hearing outcome after vestibular schwannoma surgery in men: a subgroup analysis of a randomized multicenter phase III trial.

A 2016 published randomized multicenter phase III trial of prophylactic nimodipine treatment in vestibular schwannoma surgery showed only a tendency for higher hearing preservation rates in the treatment group. Gender was not included in statistical analysis at that time. A retrospective analysis of the trial considering gender, preoperative hearing, and nimodipine treatment was performed. The treatment group received parenteral nimodipine from the day before surgery until the seventh postoperative day. The control group was not treated prophylactically. Cochlear nerve function was determined by pure-tone audiometry with speech discrimination preoperatively, during in-patient care, and 1 year after surgery and classified according to the Gardner-Robertson grading scale (GR). Logistic regression analysis showed a statistically significant effect for higher hearing preservation rates (pre- and postoperative GR 1-4) in 40 men comparing the treatment (n = 21) and the control (n = 19) groups (p = 0.028), but not in 54 women comparing 27 women in both groups (p = 0.077). The results were also statistically significant for preservation of postoperative hearing with pre- and postoperative GR 1-3 (p = 0.024). There were no differences in tumor sizes between the treatment and the control groups in men, whereas statistically significant larger tumors were observed in the female treatment group compared with the female control group. Prophylactic nimodipine is safe, and an effect for hearing preservation in 40 men with preoperative hearing ability of GR 1-4 was shown in this retrospective investigation. The imbalance in tumor size with larger tumors in females of the treatment group may falsely suggest a gender-related effect. Further investigations are recommended to clarify whether gender has impact on nimodipine's efficacy.

Interobserver variability of the House-Brackmann facial nerve grading system for the analysis of a randomized multi-center phase III trial.

BACKGROUND: Evidence of a high interobserver variability of the subjective House-Brackmann facial nerve grading system (HBGS) would justify cost- and time-consuming technological enhancements of objective classifications for facial nerve paresis. METHOD: A total of 112 patients were recruited for a randomized multi-center trial to investigate the efficacy of prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery. For the present investigation both treatment groups were pooled for the assessment of facial nerve function preoperatively, in the early postoperative course and 1 year after the surgery. Facial nerve function was documented photographically at rest and in motion and classified according to the HBGS by three independent observers (neurosurgeon, neurologist, ENT) and by the investigator of each center. RESULTS: Interobserver variability was considerably different with respect to the three time points depending upon the severity of facial nerve paresis. Preoperative facial nerve function was normal or only mildly impaired (HB grade I or II) and was assessed consistently in 97%. Facial nerve function deteriorated during the early postoperative course and was subsequently documented without dissent in only 36%, with one grade difference in 45%, two grade difference in 17% and three grade difference in 2%. One year after surgery, facial nerve function predominantly improved resulting in a consistent assessment in 66%. Differing ratings were observed in 34% with one grade deviation in 88% and of two grades in 12%. Patients with differing ratings of two or more grades exhibited considerably worse facial nerve function (p < 0.001). CONCLUSIONS: The HBGS produced comparable results between different observers in patients with normal or only mildly impaired facial nerve function. Interobserver variability increased depending on the severity of facial nerve paresis. The results suggest that the HBGS does not promote uniformity of reporting and comparison of outcomes in patients with moderate or severe facial nerve paresis.

A critical comparison between the semisitting and the supine positioning in vestibular schwannoma surgery: subgroup analysis of a randomized, multicenter trial.

OBJECTIVE: Patient positioning in vestibular schwannoma (VS) surgery is a matter of ongoing discussion. Factors to consider include preservation of cranial nerve functions, extent of tumor resection, and complications. The objective of this study was to determine the optimal patient positioning in VS surgery. METHODS: A subgroup analysis of a randomized, multicenter trial that investigated the efficacy of prophylactic nimodipine in VS surgery was performed to investigate the impact of positioning (semisitting or supine) on extent of resection, functional outcomes, and complications. The data of 97 patients were collected prospectively. All procedures were performed via a retrosigmoid approach. The semisitting position was chosen in 56 patients, whereas 41 patients were treated while supine. RESULTS: Complete resection was obtained at a higher percentage in the semisitting as compared to the supine position (93% vs 73%, p = 0.002). Logistic regression analysis revealed significantly better facial nerve function in the early postoperative course in the semisitting group (p = 0.004), particularly concerning severe facial nerve paresis (House-Brackmann grade IV or worse; p = 0.002). One year after surgery, facial nerve function recovered. However, there was still a tendency for better facial nerve function in the semisitting group (p = 0.091). There were no significant differences between groups regarding hearing preservation rates. Venous air embolism with the necessity to terminate surgery occurred in 2 patients in the semisitting position (3.6%). Supplementary analysis with a 2-tailed permutation randomization with 10,000 permutations of treatment choice and a propensity score matching showed either a tendency or significant results for better facial nerve outcomes in the early postoperative course and extent of resection in the semisitting group. CONCLUSIONS: Although the results of the various statistical analyses are not uniform, the data indicate better results concerning both a higher rate of complete removal (according to the intraoperative impression of the surgeon) and facial nerve function after a semisitting as compared to the supine position. These advantages may justify the potential higher risk for severe complications of the semisitting position in VS surgery. The choice of positioning has to consider all individual patient parameters and risks carefully.

Prophylactic nimodipine treatment and improvement in hearing outcome after vestibular schwannoma surgery: a combined analysis of a randomized, multicenter, Phase III trial and its pilot study.

OBJECTIVE In clinical routines, neuroprotective strategies in neurosurgical interventions are still missing. A pilot study (n = 30) and an analogously performed Phase III trial (n = 112) pointed to a beneficial effect of prophylactic nimodipine and hydroxyethyl starch (HES) in vestibular schwannoma (VS) surgery. Considering the small sample size, the data from both studies were pooled. METHODS The patients in both investigator-initiated studies were assigned to 2 groups. The treatment group (n = 70) received parenteral nimodipine (1-2 mg/hour) and HES (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 72) was not treated prophylactically. Facial and cochlear nerve functions were documented preoperatively, during the inpatient care, and 1 year after surgery. RESULTS Pooled raw data were analyzed retrospectively. Intent-to-treat analysis revealed a significantly lower risk for hearing loss (Class D) 12 months after surgery in the treatment group compared with the control group (OR 0.46, 95% CI 0.22-0.97; p = 0.04). After exclusion of patients with preoperative Class D hearing, this effect was more pronounced (OR 0.38, 95% CI 0.17-0.83; p = 0.016). Logistic regression analysis adjusted for tumor size showed a 4 times lower risk for hearing loss in the treatment group compared with the control group (OR 0.25, 95% CI 0.09-0.63; p = 0.003). Facial nerve function was not significantly improved with treatment. Apart from dose-dependent hypotension (p < 0.001), the study medication was well tolerated. CONCLUSIONS Prophylactic nimodipine is safe and may be recommended in VS surgery to preserve hearing. Prophylactic neuroprotective treatment in surgeries in which nerves are at risk seems to be a novel and promising concept. Clinical trial registration no.: DRKS 00000328 ( https://drks-neu.uniklinik-freiburg.de/drks_web/ ).

Stability of hearing preservation and regeneration capacity of the cochlear nerve following vestibular schwannoma surgery via a retrosigmoid approach.

OBJECTIVE The purpose of this research was to examine the stability of long-term hearing preservation and the regeneration capacity of the cochlear nerve following vestibular schwannoma (VS) surgery in a prospective study. METHODS A total of 112 patients were recruited for a randomized multicenter trial between January 2010 and April 2012 to investigate the efficacy of prophylactic nimodipine treatment versus no prophylactic nimodipine treatment in VS surgery. For the present investigation, both groups were pooled to compare hearing abilities in the early postoperative course and 1 year after the surgery. Hearing was examined using pure-tone audiometry with speech discrimination, which was performed preoperatively, in the early postoperative course, and 12 months after surgery and was subsequently classified by an independent otorhinolaryngologist using the Gardner-Robertson classification system. RESULTS Hearing abilities at 2 time points were compared by evaluation in the early postoperative course and 1 year after surgery in 102 patients. The chi-square test showed a very strong association between the 2 measurements in all 102 patients (p < 0.001) and in the subgroup of 66 patients with a preserved cochlear nerve (p < 0.001). CONCLUSIONS There is no significant change in cochlear nerve function between the early postoperative course and 1 year after VS surgery. The result of hearing performance, as evaluated by early postoperative audiometry after VS surgery, seems to be a reliable prognosticator for future hearing ability. Clinical trial registration nos.: 2009-012088-32 ( clinicaltrialsregister.eu ) and DRKS 00000328 ("AkNiPro," drks-neu.uniklinik-freiburg.de/drks_web/ ).

Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial.

OBJECTIVE: A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. METHODS: An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1-2 mg/hr) and hydroxyethyl starch (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. RESULTS: Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34-3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18-1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed. CONCLUSIONS: There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the odds ratios may suggest but do not prove a clinically relevant effect of the safe study medication on the preservation of cochlear nerve function after VS surgery. Further study is needed before prophylactic nimodipine can be recommended in VS surgery.