Atypical clinical presentations of vestibular schwannomas.

A significant number of patients with vestibular schwannomas present atypically, with none of the classical symptoms of unilateral sensorineural hearing loss, tinnitus, and/or dysequilibrium. The aim of this study is to highlight those patients with unusual clinical symptoms. STUDY DESIGN: The clinical data of all patients who presented to the vestibular schwannoma clinic at Beaumont Hospital over the past 12 years was prospectively recorded in a computerized database. This paper reviews the atypical presenting symptoms. RESULTS: Three hundred ninety-eight patients were included in this study. A total of 3.7% of patients presented with atypical symptoms only. CONCLUSION: A significant subgroup, 3.7% in our study, did not present with the audiovestibular symptoms classically associated with vestibular schwannoma. Clinician awareness of the atypical clinical symptoms may lead to earlier detection of these lesions.     

Expression of vascular endothelial growth factor and basic fibroblast growth factor in sporadic vestibular schwannomas correlates to growth characteristics.

HYPOTHESIS: Expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) may have an impact on the growth characteristics of sporadic vestibular schwannomas (VSs). BACKGROUND: Vestibular schwannoma is a benign, slow-growing neoplasm that accounts for 6% of all intracranial tumors. The biological backgrounds for neoplastic growth and especially for the various growth patterns of VS remain largely unknown. Because several angiogenic and cytotrophic factors have been described to be involved in the growth of malignant tumors, we initiated this study to examine 2 major representatives of such growth factors in VS and their possible correlation to the growth characteristics of sporadic VSs. METHODS: Surgical specimens from 17 patients with sporadic VS were examined, and the expression of 2 major angiogenic and neurotrophic factors, bFGF and VEGF, was quantitatively analyzed at the mRNA and protein levels. The microvessel density (MVD) was defined by CD31 staining. RESULTS: All tumors showed expression of bFGF and VEGF at both the mRNA and protein levels. The mRNA expression and the protein expression of both growth factors correlated positive to tumor volume, to tumor growth index, and to MVD. CONCLUSION: The bFGF and VEGF mRNA expression and the bFGF and VEGF protein expression in sporadic VS correlates to the tumour volume, to the tumor growth index, and to the MVD. This might indicate an angiogenic and neurotrophic influence of these factors and a possible involvement in the growth of sporadic VS.     

Unusual clinical presentations of vestibular schwannomas

The aim of this study is evaluate the unusual ways of initial presentation of the vestibular schwannomas. We performed a retrospective study of the patients who underwent resection of acoustic neuromas on our service, including for analysis only the cases which initial symptom was not the hearing loss. Tumor size, localization, clinical presentation, and age of the patients were considered. Nine patients present with atypical symptoms. The most common complain in this group were facial paresthesias (22,2 %). None of them complained about other otological symptoms. A significant group of patients did not present with the otological symptoms classically associated with vestibular schwannoma. Clinical knowledge of these kinds of symptoms may lead to earlier detection of these lesions.     

Immunohistochemical demonstration of vascular endothelial growth factor in vestibular schwannomas correlates to tumor growth rate

OBJECTIVE: Vascular endothelial growth factor (VEGF) is one of the most potent mediators of angiogenesis, which is a mandatory process during tumor growth. The present objectives were to determine expression of VEGF in vestibular schwannomas by immunohistochemistry and to examine a possible correlation with symptom duration, tumor size, or growth rate. STUDY DESIGN: Retrospective patient file review; immunohistochemistry and light microscopy of vestibular schwannomas removed by surgery. METHODS: Vestibular schwannomas from 18 patients were immunolabelled using a polyclonal antibody against VEGF, followed by light microscopy and blinded semiquantitation of VEGF expression. Fifteen patients had a well-defined tumor growth rate defined by repeated preoperative magnetic resonance imaging scans. RESULTS: All tumors showed expression of VEGF in the Schwann cell cytoplasm, with a more intense staining of the perinuclear region of some cells. The staining intensity varied from tumor to tumor, and semiquantitation revealed a significant correlation between VEGF expression and tumor growth rate, but not symptom duration or tumor size. CONCLUSION: VEGF is expressed in vestibular schwannomas and the level of expression correlates positively with tumor growth rate, but not with tumor size and symptom duration. We conclude that VEGF seems to be a factor involved in the growth of vestibular schwannomas.     

Incidence of vestibular schwannomas.

OBJECTIVE: To determine the incidence of vestibular schwannoma (VS) in Denmark in a period of 191/2 years. STUDY DESIGN: Retrospective review of prospective registered data on all patients with VS operated on by the translabyrinthine, lateral suboccipital, or middle cranial fossa approach, as well as patients who were allocated to the "wait-and-scan" group. METHODS: Charts were reviewed and tabulated for age, extrameatal tumor extension, and date of diagnosis. The available data were divided into three periods: June 1976 to June 1983, July 1983 to June 1990, and July 1990 to December 1995. RESULTS: The number of newly diagnosed tumors in the first period was 278, corresponding to an incidence of 7.8 tumors/million population per year; in the second period 337, corresponding to an incidence of 9.4 tumors/million population per year; and in the third period 355, corresponding to an incidence of 12.4 tumors/million population per year. A significant increase in incidence of the newly diagnosed intracanalicular tumors in the second and third periods was observed. CONCLUSION: The increase in incidence of VS can probably be explained by the awareness among otolaryngologists of the diagnosis of VS and better access to computed tomography and magnetic resonance imaging scans. The observed increase in the diagnosis of the small and intrameatal tumor creates a clinical dilemma, whether to operate on tumors in this early stage or to allocate patients to the wait-and-scan group. This problem will still be relevant in the upcoming years, since the incidence of intrameatal and small VS is expected to increase.     

Cyclin D1 expression and histopathologic features in vestibular schwannomas.

OBJECTIVE: To evaluate cyclin D1 expression in vestibular schwannoma and its relationship with histologic, clinical, and radiologic features. PATIENTS: Twenty-one patients with histologically confirmed vestibular schwannoma. INTERVENTION: Immunohistochemistry analysis was performed with anticyclin D1. Histopathologic features studied included Antoni pattern and nuclear and stromal degenerative changes. Clinical charts, audiometric data, and magnetic resonance imaging characteristics were reviewed. MAIN OUTCOME MEASURES: Cyclin D1 expression and its association with histologic, clinical, and radiologic findings. RESULTS: Cyclin D1 expression was found in 52% of cases. Cyclin D1 expression was more frequent in right-sided tumors (p = 0.02) and in tumors with nuclear degenerative changes (p < 0.0001). Patients with negative cyclin D1 expression had longer duration of deafness (p = 0.02) and higher 2,000-Hz hearing thresholds (p = 0.04) than cyclin D1+ patients. CONCLUSION: Cyclin D1 expression, present in nearly half of the cases, may play a role in the development of these tumors. Further studies are needed to fully understand the contributions of histopathologic and immunohistochemical factors to vestibular schwannoma biological activity.     

A clinical study of vestibular schwannomas in type 2 neurofibromatosis

All 13 patients with neurofibromatosis 2 (NF2) who presented over a period of 17 years at the Institute of Neurological Sciences, Glasgow were reviewed and compared to patients with sporadic vestibular schwannomas. The NF2 patients presented at a younger age than those with sporadic vestibular schwannomas. A significant number had normal pure tone audiograms and a small number also had normal auditory brainstem responses at presentation. Vestibular schwannomas in NF2 patients grow more often and more rapidly than sporadic unilateral ones. They are more liable to infiltrate the cochlear and facial nerves making hearing and facial nerve preservation more difficult to achieve. Because the relatives of these patients often have normal audiograms and normal auditory brain stem responses in the presence of a schwannoma, our recommended method of screening of relatives of NF2 patients is magnetic resonance image scanning with Gd-DTPA enhancement.     

Sublocalization and volumetric growth pattern of intracanalicular vestibular schwannomas

OBJECTIVE: None of several previous reports on the growth pattern of vestibular schwannomas (VS) have dealt with the sublocalization and volumetric growth pattern of intracanalicular tumors. This paper reports such data from 196 patients. STUDY DESIGN: All VS patients have been registered prospectively at one center in Denmark since 1975. Data on intracanalicular tumors were drawn from the database, yielding 196 patients with a diagnostic and at least one control magnetic resonance imaging scan. All images were retrieved and the tumor sublocalization, size, and growth rate determined. RESULTS: The majority (50%) of the tumors was located centrally in the internal auditory canal (IAC), whereas 31% were porus-near and 19% fundus-near. Of the 196 tumors, 88 (45%) displayed growth, 20 (10%) shrinkage, and 88 (45%) remained unchanged. Thirty-eight (19%) tumors grew to extrameatal extension. Growth occurred only within 5 years after diagnosis. In the 88 growing tumors, the mean absolute growth rate was 111mm/year and the relative rate 114%/volume/year. The occurrence of IAC expansion at diagnosis was higher for tumors displaying subsequent shrinkage. Growth occurrence and rate, IAC expansion, and progression to extrameatal extension were not related to tumor sublocalization. CONCLUSION: Most intracanalicular VS are located centrally in a nonexpanded IAC at diagnosis. Growth occurs within 5 years after diagnosis in up to 45% of the tumors, although only 19% extend into the cerebellopontine angle. IAC expansion, growth occurrence, and rate are not related to tumor sublocalization. These findings justify primary observation of all purely intracanalicular tumors, unless realistic hearing preservation is intended.     

Hearing in patients with intracanalicular vestibular schwannomas

This paper reports data on the spontaneous course of hearing in 156 patients with purely intracanalicular vestibular schwannomas. The mean pure tone average (PTA) was 51 dB HL and the mean speech discrimination score (SDS) 60% at diagnosis. The risk of a significant subsequent hearing loss (>or=10 dB PTA or >or=10% SDS) was 54% during 4.6 years of observation. Patients with normal speech discrimination at diagnosis had a significantly smaller risk of loosing hearing. The hearing loss at diagnosis and during observation was not related to age, gender, diagnostic tumor size, tumor- induced expansion of the internal auditory canal or tumor sublocalization (fundus, central or porus). However, the loss of PTA was smaller in shrinking tumors and the PTA deterioration rate correlated with the volumetric tumor growth rate. After 4.6 years observation, the PTA had increased by 14 dB to 65 dB HL, and the SDS reduced by 17% to 43%. The proportion of patients eligible for hearing preservation treatment as determined by word recognition score class I (70-100% SDS) was reduced to 28% (a 44% reduction), and by AAO-HNS class A to 9% (a 53% reduction).     

Tumor growth and audiometric change in vestibular schwannomas managed conservatively

OBJECTIVE: To prospectively define the correlation between changes in tumor volume and audiometric function in vestibular schwannomas managed conservatively. STUDY DESIGN: Prospective longitudinal study. METHODS: Twenty-one patients (age range, 15-84 y; mean age, 63.3 y) with newly diagnosed vestibular schwannomas were enrolled between 1994 and 1999 in a protocol at The Ohio State University Hospital (Columbus, OH) to evaluate the correlation between tumor volume and audiometric change during a period of observation. Patients were evaluated yearly by clinical examination, a standardized internal auditory canal magnetic resonance imaging scan with gadolinium contrast for volumetric analysis, and audiometric function testing. Demographic data, historical features, neurofibromatosis type 2 (NF2) status, initial testing results, and serial testing results were recorded. RESULTS: An increase in tumor volume occurred in 14 of the 21 patients (66%). The pattern of volumetric change was found to be extremely variable. Multiple regression analysis revealed significant correlations of changes in tumor volume with changes in pure-tone average and speech discrimination score (P < .0001 and P = .0021, respectively). Change in tumor volume had greater effect on pure-tone average and speech discrimination score in patients initially with class D audiometric function when compared with those initially in class A (P = .0083 and P = .0245, respectively). The presence of NF2 had an independent protective effect against deterioration of the pure-tone average when compared with patients without NF2 (P = .0125). CONCLUSIONS: This study demonstrated a significant correlation between a change in volume and auditory deterioration in vestibular schwannomas being managed with a trial of observation. A given change in tumor volume appeared to have a greater effect on pure-tone average and speech discrimination score as initial auditory classification declined.     

Referral patterns in vestibular schwannomas

The investigation and treatment of vestibular schwannomas is an increasingly specialized area in which major advances have been seen over recent years. The effect of these advances on the referral patterns to a centre specializing in such surgery is reviewed. The proportion of referrals with a known diagnosis has increased substantially, allowing the specialist centre to focus on appropriate management rather than diagnosis. The vast majority of vestibular schwannomas are referred by otolaryngologists. The caseload referred by neurologists or neurosurgeons have different presenting symptoms. The incidence of vestibular schwannoma in the Cambridge district is found to be 1 per 50 000 population per year. This is a higher incidence than that recorded in other studies. This may be due to a tight diagnostic strategy and the high level of clinical awareness of the local general practitioners.     

Our surgical experience with large vestibular schwannomas

Our aim is to remove large vestibular schwannomas (VS) radically with minimal morbidity. Usually, these tumours cannot not be treated by irradiation. In the years 1997-2003, 69 VS were operated in the Department of Otorhinolaryngology, Head and Neck Surgery of the First Medical Faculty in Prague, Czech Republic. Prevailing majority of these tumours were of the 4th grade (House classification), compressing the brainstem. Six patients in the group suffered from neurofibromatosis 2, in five cases the patients were indicated for neurosurgery due to rapid tumour growth after previous irradiation. All tumours were radically removed using a retromastoid osteoplastic and translab approach with an intraoperative nerve monitoring. Good function of the facial nerve was achieved in 90%. The nerve had to be resutured in 4 cases with consequent satisfactory results, cross anatomosis was not performed. Hearing function was preserved in 8% of patients only. In 6 patients with neurofibromatosis 2, the auditory brainstem implant (ABI) was used to preserve hearing. This study demonstrates that a radical removal of large vestibular schwannomas is possible using a minimally invasive surgical technique and peroperative nerve monitoring with a good impact on quality of life. Auditory brainstem implants bring a new chance of hearing after tumour removal in patients with NF2.     

Postoperative imaging and follow-up of vestibular schwannomas.

OBJECTIVE: No standards exist regarding patient follow-up after complete vestibular schwannoma resection. We surveyed neurotologists and neurosurgeons to determine practice patterns. STUDY DESIGN: A nonrandomized sample of American Neurotology Society and North American Skull Base Society members was surveyed. Questions concerned years in practice, experience with vestibular schwannoma surgery, and postoperative follow-up algorithms given the scenario of complete gross tumor removal. Data were collected, tallied, and statistically analyzed. SETTING: Academic and private practice neurotologists and neurosurgeons. SUBJECTS: Nonrandom sample of American Neurotology Society and North American Skull Base Society members. MAIN OUTCOME MEASURES: Number of postoperative magnetic resonance imaging scans, timing of magnetic resonance imaging scans, timing of final magnetic resonance imaging scan, timing of final visit, and variability between specialties. RESULTS: Four hundred ninety-eight surveys were sent and 135 were returned (27.1%). The average number of postoperative magnetic resonance imaging scans was 3.6 for neurotologists (range, 1-11) and 5.6 for neurosurgeons (range, 1-13). This was statistically significant (p >0.001). There was no correlation between number of magnetic resonance imaging scans and either years in practice or tumor experience. Average length of follow-up varied greatly (1 year to lifetime) but was most commonly 5 years. Eight percent of neurotologists varied their postoperative routine on the basis of surgical approach, whereas none of the neurosurgeons did. CONCLUSION: There remains no standard postoperative imaging algorithm for patients after complete vestibular schwannoma resection.     

Management of growing vestibular schwannomas

Conservative management of small vestibular schwannomas is frequently proposed as most tumours do not grow. Anyway, tumour growth is reported in 30–40 % of the cases, so that surgery is consequently generally proposed. We primarily observed 161 patients affected by unilateral vestibular schwannomas. All patients were examined by means of gadolinium-enhanced magnetic resonance imaging scans. Tumour growth was recorded in 58 cases (35.8 %) and these subjects set up the group of study. Twenty-two (37.9 %) patients were surgically treated; tumour was always completely removed, all patients had normal facial function after surgery and only one patient suffered from a major complication (cerebellar haematoma). Fourteen patients (24.1 %) were submitted to radiotherapy, while one patient was lost at follow-up and another one died because of other medical reasons. Finally, 20 (34.5 %) subjects continued to be observed for different reasons. The mean follow-up period after identification of growth was 6.1 years. Nine tumours continued to grow, nine tumours stopped growing, one tumour grew and then regressed in size and one tumour decreased. Sixty percent of patients with useful hearing at diagnosis preserved it during the entire observation period. In conclusion, most of VS do not grow; in case of tumour growth, a surgical procedure may be suggested and the outcomes are not negatively influenced by the delay of the procedure. But in some cases, patients can still follow the “wait and scan” policy. In fact, only less than half of the growing tumours continued to grow. Moreover, most of the patients continued to retain a useful hearing.     

Postoperative vestibular-evoked myogenic potentials in cases with vestibular schwannomas

Although still the subject of discussion, vestibular-evoked myogenic potentials (VEMPs) have been considered to reflect the function of the saccular and, more recently, the cochlear tracts. To accurately determine the precise afferent pathway carrying VEMPs, we studied the outcomes of VEMPs and other examinations in patients with unilateral vestibular schwannomas. Eleven patients with unilateral vestibular schwannomas resected using a middle cranial fossa approach were included in the study. Patients underwent pure-tone threshold audiometry, caloric tests and analysis of auditory brainstem responses (ABRs) and VEMPs pre- and postoperatively. The results were compared with those obtained in patients with intact superior or inferior vestibular and cochlear nerves. Among the 11 patients studied, 4 retained their VEMPs postoperatively. Three of the 10 patients with inferior vestibular schwannomas exhibited normal VEMPs, preserved hearing levels (20 dB HL) and anatomically intact superior vestibular nerves. In all of these cases, ABRs more closely correlated with VEMPs than with caloric responses. In one of the cases with inferior vestibular schwannomas, VEMPs were preserved postoperatively and VEMP latencies were shortened, which indicates the preoperative presence of a conduction block in either the cochlear or superior vestibular nerve. VEMPs may be conducted in both the superior vestibular and cochlear nerves, as well as in the inferior vestibular nerve. Thus, evaluation of saccular nerve function should be performed carefully, especially in cases where hearing is preserved. It appears that cochlear conduction may proceed along two pathways, one direct and the other via the brainstem, but this remains to be verified.     

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.     

Inner ear extension of vestibular schwannomas

OBJECTIVE: Inner ear extension of vestibular schwannomas (VSs) is a rare finding but has important clinical implications. This report reviews the treatment options and presents the experience of the Gruppo Otologico, Piacenza, Italy, in this field. STUDY DESIGN: Case report and literature review. METHODS: Five cases of VSs with inner ear extension were surgically removed. In all of them, the cochlea was partially or completely invaded by the lesion. RESULTS: In 4 cases, the inner ear extension was preoperatively identified on magnetic resonance imaging, and the surgical removal was planned through a transotic approach. In the last case, the cochlear invasion was not detected preoperatively, and the lesion was removed during a second surgery performed to seal a cerebrospinal fluid fistula. CONCLUSIONS: VSs with inner ear extension should be distinguished from pure intralabyrinthine schwannomas because of differences in clinical significance. Cochlear involvement is more frequent than vestibular involvement and is often accompanied by a dead ear. Dead ear caused by small VSs should alert the surgeon to the possibility of a cochlear extension. The presence of an intracochlear involvement requires the adoption of an approach that allows control of the cochlear turns, and we found the transotic approach to be the most suitable. Undetected cochlear extensions that are left in place may grow with time.     

Quality of life in patients with vestibular schwannomas managed conservatively

Since the era of magnetic resonance imaging (MRI) scanning, vestibular schwannomas are being diagnosed earlier, growth has been shown to be static in up to 70% of cases and patients have admitted to a reduced quality of life following acoustic neuroma surgery. The aim of this study was to assess the quality of life in patients with vestibular schwannomas managed conservatively. Fifty patients with a vestibular schwannoma were identified who were being managed by interval MRI scanning. Fifty patients attending the general otolaryngology clinic with similar symptoms were prospectively recruited. Each group was assessed using the short form 36 (SF-36) health survey. Both groups were adequately age and sex matched and the SF-36 scores were comparable across all eight health domains.