BACKGROUND Profound hearing loss is a serious complication of neurofibromatosis type 2, a genetic condition associated with bilateral vestibular schwannomas, benign tumors that arise from the eighth cranial nerve. There is no medical treatment for such tumors. METHODS We determined the expression pattern of vascular endothelial growth factor (VEGF) and three of its receptors, VEGFR-2, neuropilin-1, and neuropilin-2, in paraffin-embedded samples from 21 vestibular schwannomas associated with neurofibromatosis type 2 and from 22 sporadic schwannomas. Ten consecutive patients with neurofibromatosis type 2 and progressive vestibular schwannomas who were not candidates for standard treatment were treated with bevacizumab, an anti-VEGF monoclonal antibody. An imaging response was defined as a decrease of at least 20% in tumor volume, as compared with baseline. A hearing response was defined as a significant increase in the word-recognition score, as compared with baseline. RESULTS VEGF was expressed in 100% of vestibular schwannomas and VEGFR-2 in 32% of tumor vessels on immunohistochemical analysis. Before treatment, the median annual volumetric growth rate for 10 index tumors was 62%. After bevacizumab treatment in the 10 patients, tumors shrank in 9 patients, and 6 patients had an imaging response, which was maintained in 4 patients during 11 to 16 months of follow-up. The median best response to treatment was a volumetric reduction of 26%. Three patients were not eligible for a hearing response; of the remaining seven patients, four had a hearing response, two had stable hearing, and one had progressive hearing loss. There were 21 adverse events of grade 1 or 2. CONCLUSIONS VEGF blockade with bevacizumab improved hearing in some, but not all, patients with neurofibromatosis type 2 and was associated with a reduction in the volume of most growing vestibular schwannomas.

Objective: Early studies suggest that bevacizumab treatment can result in tumor shrinkage and hearing improvement for some patients with neurofibromatosis 2 (NF2). The aim of this study was to report extended follow-up in a larger cohort of similarly treated patients.Study Design: Retrospective study. Setting: Tertiary referral centerPatients: 31 consecutive NF2 patients who received bevacizumab for progressive vestibular schwannomas.Main Outcome Measure: Hearing improvement, defined as an improvement in word recognition score above the 95% critical difference compared with baseline, and radiographic response, defined as a ≥20% decrease in tumor volume compared with baseline. Results:The median age was 26 years (range, 12-73). The median volumetric tumor growth rate before treatment was 64% per year. At the time of analysis, the median duration of treatment was 14 months (range, 6-41) with a total of 45 patient-years of follow up. A hearing response occurred in 13/23 (57%) evaluable patients, and a radiographic response in 17/31 (55%) of target vestibular schwannomas. The median time to response was 3 months for both endpoints. The only clinical or radiographic feature at baseline that correlated with change in tumor volume at 3 months was the mean apparent diffusion coefficient (ADC) value, a radiologic marker of edema (p=0.036). 90% of patients had stable or improved hearing after 1 year of treatment and 61% at 3 years. 88% of patients had stable or decreased tumor size after 1 year of treatment and 54% at 3 years. Overall, treatment was well tolerated.Conclusion: Bevacizumab treatment was followed by hearing improvement and tumor shrinkage in over 50% of progressive vestibular schwannomas in NF2 patients. Stable or 2 improved hearing was retained in the majority of patients.3

Norrie disease is an X-linked recessive syndrome of blindness, deafness, and mental retardation. A knock-out mouse model with an Ndp gene disruption was studied. We examined the hearing phenotype, including audiological, histological, and vascular evaluations. As is seen in humans, the mice had progressive hearing loss leading to profound deafness. The primary lesion was localized to the stria vascularis, which houses the main vasculature of the cochlea. Fluorescent dyes showed an abnormal vasculature in this region and eventual loss of two-thirds of the vessels. We propose that one of the principal functions of norrin in the ear is to regulate the interaction of the cochlea with its vasculature.

Application of steroid medication significantly improves the recovery outcomes in cases of Severe Sudden Sensorineural Hearing Loss.