The aim of this study was to evaluate the clinical results and surgical outcomes of cystic vestibular schwannomas (VSs) with fluid-fluid levels.
Forty-five patients with cystic VSs and 86 with solid VSs were enrolled in the study. The patients in the cystic VSs were further divided into those with and without fluid-fluid levels. The clinical and neuroimaging features, intraoperative findings, and surgical outcomes of the 3 groups were retrospectively compared.
Peritumoral adhesion was significantly greater in the fluid-level group (70.8%) than in the nonfluid-level group (28.6%) and the solid group (25.6%; p < 0.0001). Complete removal of the VS occurred significantly less in the fluid-level group (45.8%, 11/24) than in the nonfluid-level group (76.2%, 16/21) and the solid group (75.6%, 65/86; p = 0.015). Postoperative facial nerve function in the fluid-level group was less favorable than in the other 2 groups; good/satisfactory facial nerve function 1 year after surgery was noted in 50.0% cases in the fluid-level group compared with 83.3% cases in the nonfluid-level group (p = 0.038).
Cystic VSs with fluid-fluid levels more frequently adhered to surrounding neurovascular structures and had a less favorable surgical outcome. A possible mechanism of peritumoral adhesion is intratumoral hemorrhage and consequent inflammatory reactions that lead to destruction of the tumor-nerve barrier. These findings may be useful in predicting surgical outcome and planning surgical strategy preoperatively.
The aim of this study was to perform an accurate analysis of changes in hearing in patients with vestibular schwannoma (VS) who have undergone Gamma Knife surgery (GKS) and distinguish the impact of radiosurgery from the natural course of hearing deterioration due to the tumor itself.
This study was a retrospective review of prospectively collected patient data. A group of 154 patients with unilateral nonsurgically treated VS was conservatively monitored for more than 6 months and then treated with GKS between July 1997 and September 2005. They were followed up with serial clinical examination, MRI, and audiometry. The annual hearing decrease rate (AHDR) was measured before and after radiosurgery, and the possible prognostic factors for hearing preservation were investigated.
The mean dose prescribed to the tumor margins was 12.1 Gy. The mean radiological follow-up period after GKS was 60 months (range 7–123 months). The tumor control rate was 94.8%, and 8 patients underwent subsequent intervention due to tumor progression. The mean audiological follow-up times before and after GKS were 22 and 52 months, respectively. The mean AHDRs before and after GKS were 5.39 dB/year (95% CI 3.31–7.47 dB/year) and 3.77 dB/year (95% CI 3.13–4.40 dB/year), respectively (p > 0.05). The mean pre- and post-GKS AHDRs in patients who initially had Gardner-Robertson (GR) Class I hearing were −0.57 dB/year (95% CI −2.95 to 1.81 dB/year) and 3.59 dB/year (95% CI 2.52–4.65 dB/year), respectively (p = 0.007). The mean pre- and post-GKS AHDRs in patients who initially had GR Class II hearing were 5.09 dB/year (95% CI 1.36–8.82 dB/year) and 4.98 dB/year (95% CI 3.86–6.10 dB/year), respectively (p > 0.05). A subgroup of 80 patients had both early and late post-intervention AHDR assessment (with early referring to the period from GKS to the assessment closest to the 2-year follow-up point and late referring to the period from that assessment to the most recent one); in these patients, the mean early post-GKS AHDR was 5.86 dB/year (95% CI 4.25–7.50 dB/year) and the mean late post-GKS AHDR was 1.86 dB/year (95% CI 0.77–2.96 dB/year) (p < 0.001). A maximum cochlear dose of less than 4 Gy was found to be the sole prognostic factor for hearing preservation.
The present study demonstrated the absence of an increase in AHDR after radiosurgery as compared with the preoperative AHDR. There was even a trend indicating a reduction in the annual hearing loss after radiosurgery over the long term. To fully elucidate a possible protective effect of radiosurgery, longer-term follow-up with a larger group of patients will be required.
Angiogenesis and the platelet-derived growth factor (PDGF) pathway are active in the pathogenesis of vestibular schwannomas (VSs). The purpose of this study was to test whether imatinib mesylate (Gleevec), a PDGF receptor (PDGFR) blocker, reduces angiogenic capacity in sporadic VS and in VS associated with neurofibromatosis Type 2 (NF2) using a corneal angiogenesis assay.
From 121 VS tissue samples stored in the tumor bank at the Marmara University Institute of Neurological Sciences, 10 samples (6 from sporadic cases, 4 from NF2-associated cases) were selected at random for use in this study. Expression of PDGF-A and PDGF-B and their receptors was evaluated in sporadic and NF2-associated VS as well as in glioblastoma (GBM) and normal brain tissue by means of immunohistochemistry and Western blot analysis. Corneal angiogenesis assay was then used to evaluate the angiogenic capacity of tissue specimens from sporadic and NF2-associated VS with and without imatinib treatment as well as positive and negative controls (GBM and normal brain tissue).
The angiogenic potential of the sporadic and NF2-associated VS tumor tissue differed significantly from that of the positive and negative control tissues (p <0.05). Furthermore, NF2-associated VS showed significantly lower angiogenic potential than sporadic VS (p <0.05). Imatinib treatment significantly reduced the angiogenic potential in both the sporadic VS and the NF2-associated VS groups. The level of PDGF-A and PDGFR-α as well as PDGF-B and PDGFR-β expression in sporadic VS and NF2-associated VS also differed significantly (p <0.05) from the levels in controls. Additionally the level of PDGFR-β was significantly higher in sporadic VS than in NF2-associated VS (p <0.05).
The findings of this study indicate that NF2-associated VS has significantly more angiogenic potential than sporadic VS and normal brain tissue. Additionally, imatinib reduces the angiogenic activity of both sporadic and NF2-associated VS. The authors conclude that imatinib may be a potential treatment for VS, especially for NF2-associated lesions that cannot be cured with resection or radiosurgery.
Small vestibular schwannomas (VSs) are often conservatively managed and treated only upon growth. Growth is usually reported in mm/year, but describing the growth of a 3D structure by a single diameter has been questioned. As a result, VS growth dynamics should be further investigated. In addition, baseline clinical parameters that could predict growth would be helpful. In this prospective study the authors aimed to describe growth dynamics in a cohort of conservatively managed VSs. They also compared different growth models and evaluated the ability of baseline parameters to predict future growth.
Between 2000 and 2006, 178 consecutive patients with unilateral de novo small-sized VSs identified among the Norwegian population of 4.8 million persons were referred to a tertiary care center and were included in a study protocol of conservative management. Tumor size was defined by MR imaging–based volume estimates and was recorded along with clinical data at regular visits. Mixed-effects models were used to analyze the relationships between observations. Three growth models were compared using statistical diagnostic tests: a mm/year–based model, a cm3/year–based model, and a volume doubling time (VDT)-based model. A receiver operating characteristic curve analysis was used to determine a cutoff for the VDT-based model for distinguishing growing and nongrowing tumors.
A mean growth rate corresponding to a VDT of 4.40 years (95% CI 3.49–5.95) was found. Other growth models in this study revealed mean growth rates of 0.66 mm/year (95% CI 0.47–0.86) and 0.19 cm3/year (95% CI 0.12–0.26). Volume doubling time was found to be the most realistic growth model. All baseline variables had p values > 0.09 for predicting growth.
Based on the actual measurements, VDT was the most correct way to describe VS growth. The authors found that a cutoff of 5.22 years provided the best value to distinguish growing from nongrowing tumors. None of the investigated baseline predictors were usable as predictors of growth.
An increasing number of patients with vestibular schwannomas (VSs) are being treated with radiosurgery. Treatment failure or secondary regrowth after radiosurgery, however, has been observed in 2%–9% of patients. In large tumors that compress the brainstem and in patients who experience rapid neurological deterioration, surgical removal is the only reasonable management option.
The authors evaluated the relevance of previous radiosurgery for the outcome of surgery in a series of 28 patients with VS. The cohort was further subdivided into Group A (radiosurgery prior to surgery) and Group B (partial tumor removal followed by radiosurgery prior to current surgery). The functional and general outcomes in these 2 groups were compared with those in a control group (no previous treatment, matched characteristics).
There were 15 patients in Group A, 13 in Group B, and 30 in the control group. The indications for surgery were sustained tumor enlargement and progression of neurological symptoms in 12 patients, sustained tumor enlargement in 15 patients, and worsening of neurological symptoms without evidence of tumor growth in 1 patient. Total tumor removal was achieved in all patients in Groups A and B and in 96.7% of those in the control group. There were no deaths in any group. Although no significant differences in the neurological morbidity or complication rates after surgery were noted, the risk of new cranial nerve deficits and CSF leakage was highest in patients in Group B. Patients who underwent previous radiosurgical treatment (Groups A and B) tended to be at higher risk of developing postoperative hematomas in the tumor bed or cerebellum. The rate of facial nerve anatomical preservation was highest in those patients who were not treated previously (93.3%) and decreased to 86.7% in the patients in Group A and to 61.5% in those in Group B. Facial nerve function at follow-up was found to correlate to the previous treatment; excellent or good function was seen in 87% of the patients from the control group, 78% of those in Group A, and 68% of those in Group B.
Complete microsurgical removal of VSs after failed radiosurgery is possible with an acceptable morbidity rate. The functional outcome, however, tends to be worse than in nontreated patients. Surgery after previous partial tumor removal and radiosurgery is most challenging and related to worse outcome.
Vestibular schwannomas are slow-growing tumors of the myelin-forming cells that cover cranial nerve VIII. The treatment options for patients with vestibular schwannoma include active observation, surgical management, and radiotherapy. However, the optimal treatment choice remains controversial.
We have reviewed the available data and summarized the radiotherapeutic options, including single-session stereotactic radiosurgery, fractionated conventional radiotherapy, fractionated stereotactic radiotherapy, and proton beam therapy.
The comparisons of the various radiotherapy modalities have been based on single-institution experiences, which have shown excellent tumor control rates of 91–100%. Both stereotactic radiosurgery and fractionated stereotactic radiotherapy have successfully improved cranial nerve V and VII preservation to >95%. The mixed data regarding the ideal hearing preservation therapy, inherent biases in patient selection, and differences in outcome analysis have made the comparison across radiotherapeutic modalities difficult. Early experience using proton therapy for vestibular schwannoma treatment demonstrated local control rates of 84–100% but disappointing hearing preservation rates of 33–42%. Efforts to improve radiotherapy delivery will focus on refined dosimetry with the goal of reducing the dose to the critical structures.
As future randomized trials are unlikely, we suggest regimented pre- and post-treatment assessments, including validated evaluations of cranial nerves V, VII, and VIII, and quality of life assessments with long-term prospective follow-up. The results from such trials will enhance the understanding of therapy outcomes and improve our ability to inform patients.