Arnaud Deveze

The human nose harbors a niche of olfactory ectomesenchymal stem cells displaying neurogenic and osteogenic properties.

We previously identified multipotent stem cells within the lamina propria of the human olfactory mucosa, located in the nasal cavity. We also demonstrated that this cell type differentiates into neural cells and improves locomotor behavior after transplantation in a rat model of Parkinsons disease. Yet, next to nothing is known about their specific stemness characteristics. We therefore devised a study aiming to compare olfactory lamina propria stem cells from 4 individuals to bone marrow mesenchymal stem cells from 4 age- and gender-matched individuals. Using pangenomic microarrays and immunostaining with 34 cell surface marker antibodies, we show here that olfactory stem cells are closely related to bone marrow stem cells. However, olfactory stem cells also exhibit singular traits. By means of techniques such as proliferation assay, cDNA microarrays, RT-PCR, in vitro and in vivo differentiation, we report that when compared to bone marrow stem cells, olfactory stem cells display (1) a high proliferation rate; (2) a propensity to differentiate into osseous cells; and (3) a disinclination to give rise to chondrocytes and adipocytes. Since peripheral olfactory stem cells originate from a neural crest-derived tissue and, as shown here, exhibit an increased expression of neural cell-related genes, we propose to name them olfactory ectomesenchymal stem cells (OE-MSC). Further studies are now required to corroborate the therapeutic potential of OE-MSCs in animal models of bone and brain diseases.

New perspectives for middle ear implants : First results in otosclerosis with mixed hearing loss

Middle ear implantation is an efficient procedure to restore moderate to severe sensorineural hearing loss (HL) in selected patients. Implantation of such devices requires ossicular chain integrity. Patients suffering from otosclerosis with mixed HL should be eligible for this treatment after stapes surgery with air‐bone gap closure. To address this issue, we report four cases of middle ear implantation after or during stapes surgery. Results and complications obtained with Vibrant SoundBridge, MedEl and Middle Ear Transducer, Otologics are reported. Audiologic results were similar to those obtained in cases of sensorineural HL. One case of postoperative labyrinthitis was observed.

Engraftment of human nasal olfactory stem cells restores neuroplasticity in mice with hippocampal lesions

Stem cell-based therapy has been proposed as a potential means of treatment for a variety of brain disorders. Because ethical and technical issues have so far limited the clinical translation of research using embryonic/fetal cells and neural tissue, respectively, the search for alternative sources of therapeutic stem cells remains ongoing. Here, we report that upon transplantation into mice with chemically induced hippocampal lesions, human olfactory ecto-mesenchymal stem cells (OE-MSCs) - adult stem cells from human nasal olfactory lamina propria - migrated toward the sites of neural damage, where they differentiated into neurons. Additionally, transplanted OE-MSCs stimulated endogenous neurogenesis, restored synaptic transmission, and enhanced long-term potentiation. Mice that received transplanted OE-MSCs exhibited restoration of learning and memory on behavioral tests compared with lesioned, nontransplanted control mice. Similar results were obtained when OE-MSCs were injected into the cerebrospinal fluid. These data show that OE-MSCs can induce neurogenesis and contribute to restoration of hippocampal neuronal networks via trophic actions. They provide evidence that human olfactory tissue is a conceivable source of nervous system replacement cells. This stem cell subtype may be useful for a broad range of stem cell-related studies.

European results with totally implantable carina placed on the round window: 2-year follow-up.

Objectives: First, to assess for the performance of the Carina placed on the round window at various European centers; second, to study the follow-up after 2 years and discuss limitations and technical issues; and finally, to further develop our understanding of the principles of acoustic transfer through the round window. Materials and Methods: Eleven patients were included in this retrospective study (7 women and 4 men) from 7 European tertiary referral hospitals (4 centers in France, 2 in Belgium, 1 in Spain). The mean age was 50.8 years (35-71 yr). All patients have multiple previous surgeries (>3 surgical procedures) for otosclerosis (3 patients) or chronic otitis media (8 patients), and in all cases, the stapes was not accessible due to obliteration by sclerotic tissue. Preoperative and postoperative air conduction, bone conduction, as well as aided and unaided thresholds and speech scores were measured. Results: No significant differences were observed between preoperative and postoperative air-conduction and bone-conduction pure-tone averages. The average free field functional gain obtained with the implant ranged from 22 to 42 dB at each individual frequency, with a mean of 29 ± 5 dB across all audiometric frequencies. Word recognition scores demonstrated significant differences between unaided and implant-aided conditions. Complications included 2 cases of postoperative infection (including 1 anacusis) that required explantation, and 1 case reduced initial benefit, followed by a nonfunctioning device. In 10 patients, postoperative hearing was unchanged. The 8 other patients are using their implant daily. Conclusion: These results show that this option is valid for patients with a fixed footplate and unsuccessful previous surgeries or patients who cannot benefit from a stapedotomy for anatomic reasons. In some cases, access to the round window membrane could represent a limitation. However, these promising initial results establish the need for further works with regard to 3 issues: 1) clinical data studies are needed, including a greater number of patients to confirm these preliminary results; 2) a long-term follow-up must be performed to detect any possible cochlear adverse effects, in particular, on the basilar membrane; 3) the effect of fascia interposition and tip size has to be evaluated in experimental studies.

Round Window Membrane Implantation with an Active Middle Ear Implant: A Study of the Effects on the Performance of Round Window Exposure and Transducer Tip Diameter in Human Cadaveric Temporal Bones

Objectives: To assess the importance of 2 variables, transducer tip diameter and resection of the round window (RW) niche, affecting the optimization of the mechanical stimulation of the RW membrane with an active middle ear implant (AMEI). Materials and Methods: Ten temporal bones were prepared with combined atticotomy and facial recess approach to expose the RW. An AMEI stimulated the RW with 2 ball tip diameters (0.5 and 1.0 mm) before and after the resection of the bony rim of the RW niche. The RW drive performance, assessed by stapes velocities using laser Doppler velocimetry, was analyzed in 3 frequency ranges: low (0.25–1 kHz), medium (1–3 kHz) and high (3–8 kHz). Results: Driving the RW produced mean peak stapes velocities (HEV) of 0.305 and 0.255 mm/s/V at 3.03 kHz, respectively, for the 1- and 0.5-mm tips, with the RW niche intact. Niche drilling increased the HEV to 0.73 and 0.832 mm/s/V for the 1- and 0.5-mm tips, respectively. The tip diameter produced no difference in output at low and medium frequencies; however, the 0.5-mm tip was 5 and 6 dB better than the 1-mm tip at high frequencies before and after niche drilling, respectively. Drilling the niche significantly improved the output by 4 dB at high frequencies for the 1-mm tip, and by 6 and 10 dB in the medium- and high-frequency ranges for the 0.5-mm tip. Conclusion: The AMEI was able to successfully drive the RW membrane in cadaveric temporal bones using a classical facial recess approach. Stimulation of the RW membrane with an AMEI without drilling the niche is sufficient for successful hearing outputs. However, the resection of the bony rim of the RW niche significantly improved the RW stimulation at medium and higher frequencies. Drilling the niche enhances the exposure of the RW membrane and facilitates positioning the implant tip.

Functional characterization of nonmetastatic paraganglioma and pheochromocytoma by (18) F-FDOPA PET: focus on missed lesions.

To evaluate the clinical value of 18F‐fluorodihydroxyphenylalanine (18F‐FDOPA) PET in relation to tumour localization and the patients genetic status in a large series of pheochromocytoma/paraganglioma (PHEO/PGL) patients and to discuss in detail false‐negative results.

Vestibular compensation and vestibular rehabilitation. Current concepts and new trends

The aim of this review is to present the current knowledge of the mechanisms underlying the vestibular compensation and demonstrating how the vestibular rehabilitation is conducted to help the recovery of balance function. Vestibular rehabilitation is based on improving the natural phenomenon called vestibular compensation that occurs after acute vestibular disturbance or chronic and gradual misbalance. Central compensation implies three main mechanisms namely adaptation, substitution and habituation. The compensation, aided by the rehabilitation aimed to compensate and/or to correct the underused or misused of the visual, proprioceptive and vestibular inputs involved in the postural control. As the strategy of equilibration is not corrected, the patient is incompletely cured and remains with inappropriate balance control with its significance on the risk of fall and impact on quality of life. The vestibular rehabilitation helps to correct inappropriate strategy of equilibrium or to accelerate a good but slow compensation phenomenon. Nowadays, new tools are more and more employed for the diagnosis of vestibular deficit (that may include various sources of impairment), the assessment of postural deficit, the control of the appropriate strategy as well to facilitate the efficiency of the rehabilitation especially in elderly people.

Revision Stapedotomy : Operative Findings and Hearing Results. A Prospective Study of 652 Cases From the Otology-Neurotology Database

Objective: To identify the causes of failure of primary stapes surgery and to evaluate the hearing results of revision stapes surgery in a consecutive series of 652 cases. Study Design: Prospective nonrandomized clinical study. Setting: Tertiary referral center. Patients: Six hundred thirty-four patients who underwent 652 consecutive revision stapes operations from April 1992 to December 2007 were enrolled in this study. Main Outcome Measures: Preoperative and postoperative audiometric evaluation using conventional audiometry, namely, air-bone gap (ABG), bone-conduction thresholds, and air-conduction thresholds, were assessed. Postoperative audiometry was performed at 3, 6, 9, 12, 18, and 24 months and then annually for 15 years. Results: The most frequently identified reason for primary surgery failure was incus erosion (27.6%) and prosthesis displacement (18.2%). The postoperative ABG was closed to 10 dB or less and 20 dB or less in 63.4 and 74.6% of cases, respectively. The mean 4-frequency postoperative ABG was 11.5 dB as compared with 28 dB preoperatively (mean difference, 16.5 dB; 95% confidence interval [CI], 15.1-17.9 dB, p < 0.0001). The mean 4-frequency postoperative air-conduction thresholds were 45.7 dB compared with 58.7 dB preoperatively (mean difference, 13 dB; 95% CI, 11.4-14.6 dB, p < 0.0001). The mean 4-frequency postoperative bone-conduction thresholds were 34 dB compared with 30.6 dB preoperatively (mean difference, −3.5 dB; 95% CI, −4.4 to −2.5 dB, p < 0.0001). A significant postoperative sensorineural hearing loss (>15 dB) was observed in 2.9% of cases in this series. Conclusion: Improvement of a conductive hearing loss after initial unsuccessful primary or revision stapes surgery can be accomplished with further revision but is occasionally modest.

Titanium ossicular chain replacement prostheses: Prognostic factors and preliminary functional results

OBJECTIVE To assess the efficiency of ossiculoplasty procedures with the Kurz titanium ossicular prosthesis and evaluate prognostic factors for the functional results. METHODS Retrospective chart reviews were performed for ossiculoplasty involving Kurz titanium prostheses between 2006 and 2009 in the ENT Head and Neck Department of the hôpital Nord, Marseille, France. RESULTS The population studied was 70 patients, with 37 procedures using the partial (PORP) and 33 the total ossicular replacement prosthesis (TORP). Mean follow-up was 9 months. Pre- and postoperative audiological parameters on four frequency averages (0.5, 1, 2, and 3kHz) were compared according to AAO-HNS guidelines. A postoperative air-bone gap (ABG)≤20dB was obtained in 71.43% of the patients (86.49% for PORP, and 54.55% for TORP). The mean change in ABG was 12.45dB in cholesteatomatous otitis versus 13.41dB in non-cholesteatomatous otitis. CONCLUSION Increasing the length of the ossicular prosthesis, especially TORP, may improve postoperative functional results.

Active middle ear implant application in case of stapes fixation: a temporal bone study.

Hypothesis: Driving the oval window directly with an active middle ear implant (AMEI) can produce high levels of input to the inner ear. Background: Treatment of otosclerosis bypasses the stapes with a piston that penetrates the vestibule. Although this treats the conductive component of hearing loss, it does not treat the sensorineural part, which can be improved using an additional conventional hearing aid. Active middle ear implants have been proposed to be an alternative in treating otosclerosis in cases of mixed hearing losses. Methods: Seven temporal bones were prepared to expose the stapes and round window (RW). Stapes and RW velocities were measured while driving with an AMEI the stapes head with a bell-shaped tip. The stapes footplate was then fixed with acrylic cement; fixation was confirmed through attenuated RW velocities. A cylinder tip (0.5 mm) was then used to drive the inner ear through a stapedotomy with and without interposition of fascia. Results: Driving the stapes with an AMEI produced mean maximum equivalent ear canal sound pressure levels (SPL) of 138 dB (0.25-8 kHz at 1 V [RMS]). Stapes fixation caused a ∼25-dB attenuation. Driving with a cylinder tip through the stapedotomy produced 114 dB SPL (24 dB less than normal) and 110 dB SPL (28 dB less than normal) performance with and without fascia, respectively. Performance with fascia was greater than without. Conclusion: Driving the oval window with an AMEI in a scenario of stapes fixation was demonstrated to be feasible, with performance comparable to traditional AMEI coupling to the incus or stapes. These possibilities offer new perspectives to treat mixed hearing loss in case of fixed footplate.