Quality of life in the management of small vestibular schwannomas: Observation, radiotherapy and microsurgery.

OBJECTIVE: The aim of this study was to compare quality of life (QOL) in small unilateral vestibular schwannoma (VS) patients managed by microsurgery, radiotherapy or observation. STUDY DESIGN: A retrospective chart review. METHODS: The study included a total of 142 patients with VS stage 1 or 2 according to the Koos classification and treated between January 2004 and December 2015. Microsurgery, radiotherapy and observation groups comprised 43, 46 and 53 patients, respectively. All patients completed four QOL (questionnaires: Short-Form Health Survey 36, Hearing Handicap Inventory, Tinnitus Handicap Inventory and Dizziness Handicap Inventory Short-Form). Clinical symptoms and QOL were compared among groups. RESULTS: The average time interval between management and filling in the questionnaires was 66 months. There was no difference in QOL between the three groups on any of the four questionnaires. The most debilitating symptom was vertigo for all three groups. Tinnitus was a pejorative factor in the surgery group. Hearing level was deteriorated after microsurgery but there was no significant difference between the radiotherapy group and the middle fossa approach. CONCLUSION: Patients with small VS stage 1 and 2 had similar QOL, irrespective of management by observation, radiotherapy or microsurgery. The overall predictor for long-term reduced QOL was vertigo. Vestibular rehabilitation could improve QOL in symptomatic patients.

Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G.

Our understanding of the mechanisms underlying inherited forms of inner ear deficits has considerably improved during the past 20 y, but we are still far from curative treatments. We investigated gene replacement as a strategy for restoring inner ear functions in a mouse model of Usher syndrome type 1G, characterized by congenital profound deafness and balance disorders. These mice lack the scaffold protein sans, which is involved both in the morphogenesis of the stereociliary bundle, the sensory antenna of inner ear hair cells, and in the mechanoelectrical transduction process. We show that a single delivery of the sans cDNA by the adenoassociated virus 8 to the inner ear of newborn mutant mice reestablishes the expression and targeting of the protein to the tips of stereocilia. The therapeutic gene restores the architecture and mechanosensitivity of stereociliary bundles, improves hearing thresholds, and durably rescues these mice from the balance defects. Our results open up new perspectives for efficient gene therapy of cochlear and vestibular disorders by showing that even severe dysmorphogenesis of stereociliary bundles can be corrected.

Lateral semicircular canal fistula in cholesteatoma: diagnosis and management.

The objective of this retrospective study was to present the authors' experience on the management of labyrinthine fistula secondary to cholesteatoma. 695 patients, who underwent tympanoplasty for cholesteatoma, in a University Hospital between 1993 and 2013 were reviewed, to select only those with labyrinthine fistulas. 42 patients (6%) had cholesteatoma complicated by fistula of the lateral semicircular canal (LSCC). The following data points were collected: symptoms, pre- and postoperative clinical signs, surgeon, CT scan diagnosis, fistula type, surgical technique, preoperative vestibular function and audiometric outcomes. Most frequent symptoms were unspecific, such as otorrhea, hearing loss and dizziness. However, preoperative high-resolution computed tomography predicted fistula in 88 %. Using the Dornhoffer and Milewski classification, 16 cases (38 %) were identified as stage 1, 22 (52 %) as stage II, and 4 (10 %) as stage III. The choice between open or closed surgical procedure was independent of the type of fistulae. The cholesteatoma matrix was completely removed from the fistula and immediately covered by autogenous material. In eight patients (19 %), the canal was drilled with a diamond burr before sealing with autologous tissue. After surgery, hearing was preserved or improved in 76 % of the patients. There was no statistically significant relationship between the extent of the labyrinthine fistula and the hearing outcome. In conclusion, a complete and nontraumatic removal of the matrix cholesteatoma over the fistula in a one-staged procedure and its sealing with bone dust and fascia temporalis, with sometimes exclusion of the LSCC, is a safe and effective procedure to treat labyrinthine fistula.

Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.

A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggest a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation show that the cochlear sensory hair cells and auditory pathway neurons of Pjvk(-/-) mice and patients are exceptionally vulnerable to sound. Subcellular analysis revealed that pejvakin is associated with peroxisomes and required for their oxidative-stress-induced proliferation. Pjvk(-/-) cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in Pjvk(-/-) hair cells show structural abnormalities after the onset of hearing. Noise exposure rapidly upregulates Pjvk cochlear transcription in wild-type mice and triggers peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage.

[Gene therapy for human hearing loss: challenges and promises]. / Thérapie génique des surdités humaines: défis et promesses.

Thanks to the advances accomplished in human genomics during the last twenty years, major progress has been made towards understanding the pathogenesis of various forms of congenital or acquired deafness. The identification of deafness genes, which are potential therapeutic targets, and generation and functional characterization of murine models for human deafness forms have advanced the knowledge of the molecular physiology of auditory sensory cells. These milestones have opened the way for the development of new therapeutic strategies, alternatives to conventional prostheses, hearing amplification for mild-to-severe hearing loss, or cochlear implantation for severe-to-profound deafness. In this review, we first summarize the progress made over the last decade in using gene therapy and antisense RNA delivery, including the development of new methods for cochlear gene transfer. We then discuss the potential of gene therapy for curing acquired or inherited deafness and the major obstacles that must be overcome before clinical application can be considered.