Factors which influence the facial nerve outcome in vestibular schwannoma surgery

A series of 276 patients with a unilateral vestibular schwannoma has been analysed with respect to the factors affecting post-operative facial nerve outcome. Age, tumour size, operative approach and the use of intra-operative facial nerve monitoring have been examined. The tumours were removed via either a translabyrinthine or a retrosigmoid approach. In this series increasing age and increasing tumour size were associated with a worse facial nerve outcome. The use of intra-operative facial nerve monitoring and the retrosigmoid approach were both associated with a better facial nerve outcome. Those patients having a retrosigmoid approach had a facial nerve result that was over one House grade better than those having translabyrinthine tumour removal.     

The natural history of vestibular schwannoma.

OBJECTIVE: The incidence of vestibular schwannomas (VSs) approaches 20 per million/yr. As treatment may depend on tumor growth, there is a demand of a treatment strategy based on hard data on the growth pattern of these tumors. This article reports growth data registered prospectively in 552 patients. STUDY DESIGN: Of the 1,818 consecutive patients, diagnosed with VS during the period from 1975 to 2005, 729 patients were allocated to observation by repetitive magnetic resonance imaging. At least two scans had been performed in 552 patients at the time of data analysis. Two hundred thirty patients had a tumor confined to the internal acoustic meatus, whereas 322 patients had a tumor with an extrameatal extension. Growth to extrameatal extension was the definition for growth in intrameatal tumors, whereas a largest diameter change of more than 2 mm was the criteria for growth/shrinkage of extrameatal tumors. The mean observation time was 3.6 years (range, 1-15 yr). RESULTS: Seventeen percent of the intrameatal tumors grew, whereas significantly more of the extrameatal tumors displayed growth during the period (28.9%). Growth occurred within the first 5 years after diagnosis. No correlation could be demonstrated between tumor growth rate, sex, or age. CONCLUSION: VS growth occurs within the first 5 years after diagnosis in a limited number of tumors, primarily in tumors with an extrameatal extension. We found no relation between tumor growth and sex or age. These findings justify primary observation of small tumors. A treatment strategy is proposed for this disease, focusing on the patient group allocated to observation.     

The learning curve in vestibular schwannoma surgery.

OBJECTIVE: This study aimed to examine the effect of surgical team experience on facial nerve function and complication rate in vestibular schwannoma surgery. STUDY DESIGN: The study design was a retrospective analysis of a case series. SETTING: The study was conducted at a tertiary referral center. PATIENTS: One hundred sixty consecutive patients undergoing vestibular schwannoma excision participated. INTERVENTION: Surgical excision of vestibular schwannoma via a translabyrinthine, middle cranial fossa, suboccipital, or combined approach was performed. MAIN OUTCOME MEASURES: Facial nerve function (House-Brackmann score) and complication rates including cerebrospinal fluid leak and meningitis compared by groups of 20 patients were measured. RESULTS: There was a statistically significant improvement in the number of patients achieving a House-Brackmann grade I result between the first 20 patients (35% House-Brackmann grade 1) and the ensuing 7 groups of 20 patients (74% House-Brackmann grade 1) by chi2 analysis. When considering House grades I and II together, there was no statistically significant difference in facial nerve function in the first 20 patients (80%) compared to the last 7 groups of 20 patients (88%) by Tukey's pairwise comparisons (p = 0.245). Mean tumor size was not significantly different in the groups studied (p = 0.54). The total cost of patient care declined over the study period; however, the wide case-to-case variance made it so that this trend was not statistically significant (p = 0.448). CONCLUSIONS: A learning curve of 20 patients was demonstrated by this study to have been necessary for attaining acceptable standards in the surgical removal of vestibular schwannomas by a new surgical team. The findings of this study may have implications for patient care and surgeon training.     

Fall risk, vestibular schwannoma, and anticoagulation therapy

Elderly patients with balance problems are at high risk for falls. When these same patients are also on anticoagulants, the consequences of a fall can be serious. Anticoagulant therapy increases the risk of cerebral hemorrhage. Even mild head trauma can cause a fatal cerebral hemorrhage when anticoagulants are used. However, this risk needs to be weighed against the possibility of spontaneous stroke. The decision to choose anticoagulant therapy can become even more complicated if the patient has an increased risk of falling. A case is presented of an 87-year-old female with balance problems, in part from a small unilateral vestibular schwannoma. She was also receiving Coumadin anticoagulant therapy. When she began to fall, a decision had to be made about the relative risks and benefits of Coumadin therapy. The risk/benefit calculation could change, however, depending on whether her fall risk could be improved. This article presents the diagnostic test results and medical opinions surrounding this case. The importance of assessing patients' overall situation is stressed in planning rehabilitation.     

Primary cultures of human vestibular schwannoma: selective growth of schwannoma cells.

OBJECTIVE: To establish primary vestibular schwannoma (VS) cultures that selectively favor the growth of schwannoma cells. BACKGROUND: The lack of a suitable in vitro model of human VS cells has directly limited the progress of research on tumorigenesis and therapy. The problems of establishing pure VS culture include control of fibroblast proliferation. Current efforts to extend VS cell life span using viral oncogenes, by conferring the ability to proliferate in vitro, will yield cells intrinsically different from in vivo VS tumors. Much more desirable is the ability to culture VS cells without cellular transformation. METHODS: Tumor specimens from 17 patients were processed for cell culture and grown at 37 degrees C with 5% CO2 and 100% humidity. Key modifications limiting fibroblast proliferation included using selective medium without L-valine, supplemented by Nu-Serum for at least a week; the use of cytosine arabinoside to kill contaminating fibroblasts; and using the Dulbecco modified medium, supplemented with brain-derived neurotrophic factor and 10% fetal calf serum after the initial serum-free period. RESULTS: Twelve of 17 VS were successfully cultured. The presence of schwannoma cells and the absence of fibroblasts were confirmed immunohistochemically using S100 and CD90 markers, respectively. Scanning and transmission electron microscopy demonstrated typical spindle-shaped cells and the presence of "fibrous long-spacing collagen." CONCLUSION: We describe a method for obtaining short-term, essentially fibroblast-free, primary VS cultures. Such pure VS cultures, retaining in vivo characteristics, are extremely useful as an in vitro model to study the pathobiology of schwannoma cells.     

Neurotrophic factor expression in vestibular schwannoma. An overview

The vestibular schwannoma is a benign, slow-growing neoplasm that originates from the neurolemmal sheath of the vestibular branch of the VIIIth cranial nerve. This tumor entity accounts for 6 % of all intracranial tumors and the annual incidence of newly diagnosed vestibular schwannoma is reported as 13 per million. The molecular pathogenesis of both sporadic vestibular schwannoma and those occurring in neurofibromatosis type II appears to be associated with an aberration of a tumor suppressor gene on chromosome 22q12. The biological background for the various growth patterns of vestibular schwannoma is, however, largely unknown. This differing clinical and biological behaviour of vestibular schwannoma may be explained by the presence of neurotrophic factors. The results of recent immunohistochemical studies demonstrate the co-expression of transforming growth factor (TGF)-beta 1 and glial cell line-derived neurotrophic factor (GDNF) in vestibular schwannoma and suggest a trophic synergism of both neurotrophic factors in this tumor. Moreover, expression of numerous different neurotrophic factors has been shown in studies of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), neuregulin (NRG) and erythropoietin (EPO) indicating a biological role in development, maintainance or growth of vestibular schwannoma. In this article, we summarize the findings on neurotrophic factor expression and discuss their characteristics and biological role in vestibular schwannoma.     

Merlin蛋白在听神经瘤组织中的表达与分布

目的明确听神经瘤中merlin蛋白的表达及其在细胞内的分布。方法收集临床诊断并且经过术后病理证实的听神经瘤组织石蜡包埋标本54例,用免疫组织化学方法分析merlin蛋白在肿瘤组织中的表达,取三叉神经痛和晚期梅尼埃病患者接受手术治疗术中切除的神经组织作为对照组。用Western blot方法测试肿瘤组织中merlin蛋白的电泳迁移行为。用图像分析方法计算每例患者的阳性表达率,将merlin蛋白表达阳性率与患者年龄、性别、肿瘤生长指数、肿瘤直径和临床分期进行比较。结果merlin蛋白在听神经瘤组织中有不同程度的表达,阳性率为0～87．5％,平均(46．66±5．75)％,与肿瘤生长指数之间无明显相关性,与患者年龄、性别、肿瘤直径和临床分期无明显相关性。merlin细胞内分布部位有一定差异,以细胞核内、核周分布为主,也有部分分布于细胞质中。Western blot显示在听神经瘤组织中merlin蛋白位于65 000和125 000。结论在听神经瘤组织中存在merlin蛋白的表达,其在细胞内分布部位有一定变异。听神经瘤组织中merlin蛋白可能同时与其他蛋白以复合物的形式存在。     

Incidence of vestibular schwannoma in Denmark, 1977-1995

OBJECTIVE: To establish the incidence rate of vestibular schwannomas (VS) (acoustic neuromas) in Denmark. BACKGROUND: The worldwide incidence rates of VS vary from 1 to 20 cases per million population per year. METHODS: The nationwide and population-based age-specific, sex-specific, and calendar year-specific incidence rates of VS in Denmark between 1977 and 1995 are presented. Information on cases of VS was obtained from the Danish Cancer Registry and a clinical database situated at the University Hospital of Gentofte. A total of 795 cases were reported during the period of the study. RESULTS: The incidence rate increased from 5 cases per million population per year in 1977-1981 to 10 cases in 1992-1995; the increase was from 5 to 11 cases among women and 5 to 9 cases among men. The age-specific incidence rates show that VS is rarely diagnosed in persons under 30, but the incidence rate appears to increase among women after menopause. CONCLUSION: The overall incidence rate of VS increased linearly during the study period, probably owing to the introduction of more precise diagnostic procedures, increased awareness among physicians and patients of the symptoms of VS, improved registration of benign tumors in Denmark, and the use of data from two sources.     

Effects of vestibulo-ocular reflex exercises on vestibular compensation after vestibular schwannoma surgery.

OBJECTIVE: To assess vestibular function in a large group of vestibular schwannoma patients so that we could determine whether simple vestibular exercises speed vestibular dysfunction recovery after tumor removal surgery. STUDY DESIGN: A prospective investigation of the vestibular dysfunction experienced by patients in the first 12 weeks after surgery. SETTING: Vestibular investigation unit at a tertiary referral institution. PATIENTS: Sixty-five patients with identified vestibular schwannoma referred for preoperative vestibular investigations. Thirty-two men and 33 women, with a mean age 51 years (range, 24-77 yr). INTERVENTIONS: There were 27 control patients, 30 exercise patients, and 8 patients that had balance physiotherapy. Exercise patients began simple vestibulo-ocular reflex gaze stabilization exercises 3 days after surgery. MAIN OUTCOME MEASURES: Postoperative vestibular function testing was performed at 2 to 3, 6 to 7, and 10 to 12 weeks after surgery. Objective measurements of vestibular compensation status were as follows: spontaneous nystagmus and sinusoidal harmonic acceleration asymmetry and gain values. Dizziness Handicap Inventory questionnaires were used to assess subjective perceptions. RESULTS: The main findings were reduced dispersion in vestibulo-ocular reflex asymmetry at 2 to 3 weeks, reduced mean in asymmetry at 6 to 7 weeks, less dizziness/imbalance according to the Dizziness Handicap Inventory questionnaire, and that preoperative caloric tests did not predict postoperative severity of vestibular systems. CONCLUSION: This large study provided unique evidence that a program of simple vestibular exercises and education can speed the rate of compensation after vestibular schwannoma surgery.     

Complications in translabyrinthine surgery of vestibular schwannoma

Objective: To evaluate the risk of complications associated with tumor size and patient’s age in translabyrinthine vestibular schwannoma surgery.

Methods: 700 patients with vestibular schwannoma primarily underwent translabyrinthine surgery between 1988 and 2014. Pre- and postoperative data were collected in a database and incidence of the postoperative complications cerebrospinal fluid leakage, meningitis, intracranial hemorrhage (ICH), facial nerve function and mortality were assessed and related to the tumor size and patient’s age and retrospectively evaluated.

Results: The tumor size significantly influenced the incidence of ICH and facial nerve dysfunction whereas age was correlated to facial nerve outcome.

Conclusions: The translabyrinthine approach is a safe surgical procedure with relatively low risks of complications. The tumor size was significantly associated with a higher risk of ICH and facial nerve dysfunction whereas age only influenced the facial nerve outcome.     

Change in tinnitus handicap after translabyrinthine vestibular schwannoma excision.

OBJECTIVE: To evaluate the change in tinnitus handicap after translabyrinthine vestibular schwannoma excision. STUDY DESIGN: Prospective administration of the Tinnitus Handicap Inventory (THI) preoperatively and at 3 and 12 months postoperatively. SETTING:: A tertiary referral neuro-otology clinic. PATIENTS: A total of 149 patients from a series of 170 consecutive patients who had vestibular schwannomas excised between May 1998 and July 2002 and who had completed THIs preoperatively and at 3 and 12 months postoperatively. INTERVENTIONS: Translabyrinthine excision of a unilateral sporadic vestibular schwannoma. MAIN OUTCOME MEASURES: THI scores. RESULTS: The number of patients with moderate or severe handicap was 21 (14%) in the preoperative group and 21 (14%) in the 12-month postoperative group. No significant differences in group data were found comparing (by Wilcoxon signed rank test) preoperative data with 3 months postoperative data (p = 0.09), preoperative data with 12 months postoperative data (p = 0.09), and 3 months postoperative data with 12 months postoperative data (p = 0.33). Considering group data, tinnitus handicap is neither alleviated nor exacerbated by translabyrinthine surgery. The application of the validated 20-point criteria for significant change in the status of an individual patient indicates that tinnitus handicap was worse in 10 (6.5%), unchanged in 129 (87%), and better in 10 (6.5%). CONCLUSIONS: The findings of the current study can be used during preoperative patient counseling. In particular, the clinician is now able to take an informed and positive stance about the tinnitus handicap to be expected postoperatively.     

Change in hearing handicap after translabyrinthine vestibular schwannoma excision.

OBJECTIVE: To evaluate the change in hearing handicap after translabyrinthine vestibular schwannoma excision. STUDY DESIGN: Prospective administration of the Hearing Handicap Inventory preoperatively and at 3 and 12 months postoperatively. SETTING: A tertiary referral neurootology clinic. PATIENTS: A total of 119 consecutive patients who had vestibular schwannomas excised between May 1998 and July 2002 and who had completed Hearing Handicap Inventories preoperatively and at 3 and 12 months postoperatively. INTERVENTIONS: Translabyrinthine excision of a unilateral sporadic vestibular schwannoma; pre- and postoperative hearing therapy and rehabilitation. MAIN OUTCOME MEASURES: Hearing Handicap Inventory scores. RESULTS: Sixty-one percent of patients showed no change in their hearing handicap between preoperative and 3-month postoperative measures. Fifty-eight percent showed no change between preoperative and 12-month postoperative measures. Twenty-five percent of patients had a worsening in their hearing handicap when comparing preoperative and 12-month postoperative scores, and these patients were those with a better hearing class preoperatively. Seventeen percent of patients showed an improvement in their hearing handicap over this same time period, and the reasons for this remain unclear. Neither age nor tumor size had an effect on change in hearing handicap. CONCLUSIONS: The findings of the current study can be used during preoperative patient counseling. In particular, the clinician is now able to take an informed and positive stance about the hearing handicap to be expected postoperatively.     

Immunolocalization of erythropoietin and erythropoietin receptor in vestibular schwannoma

Vestibular schwannomas constitute approximately 6% of intracranial tumors. Apart from the association with neurofibromatosis-2 (NF-2), where a defect in chromosome 22 has been identified, the pathogenesis of sporadic vestibular schwannomas is largely unknown. Very few studies have explored the role of neurotrophic growth factors in vestibular schwannoma. The objective of this study is to evaluate for the presence and pattern of EPO and EPO-R expression within vestibular schwannomas. Our hypothesis that erythropoietin (EPO) and erythropoietin receptor (EPO-R) were expressed in vestibular schwannomas was based on a recent report of rapid growth of a vestibular schwannoma in a patient undergoing preoperative EPO treatment. Using immunohistochemistry, we have demonstrated that both EPO and EPO-R are expressed in a majority of these tumors.     

听神经瘤的分子生物学研究进展

听神经瘤由于它特殊的自然病程而引起人们的重视。近10年来有关听神经瘤发病机制及其自然进程方面的分子生物学研究发现,在家族性听神经瘤病人中其基因型和表显型有较明确的关系,而散发的听神经瘤中关系目前尚未完全清楚。NF2基因的失活只在肿瘤发生的早期起作用,可能还有其他基因参与肿瘤的分化调节,进一步的研究是必要的。