Jacques Magnan

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.

A middle ear implant, the symphonix Vibrant soundbridge: Retrospective study of the first 125 patients implanted in France

Objective The Vibrant Soundbridge is an active semi-implantable middle ear implant for the rehabilitation of patients with a sensorineural hearing loss who are not able to derive adequate benefit from conventional hearing aids. A retrospective study was performed to assess the overall level of satisfaction of implanted patients and to investigate the potential determinants of postoperative success. Study Design A retrospective survey of audiological data from repeated measures and subjective data from self-assessment scales administered postoperatively was conducted to determine the degree of benefit and satisfaction for Vibrant Soundbridge implantees. Setting Twenty-one tertiary referral and teaching hospitals. Subjects The first 125 VSB implantees implanted in France between August 1997 and May 2001 were included in the study. Results No clinically significant change was observed for residual hearing postoperatively. Most patients (83%) reported they were either satisfied or very satisfied with the Vibrant Soundbridge. Analysis of correlation revealed a moderate correlation (Pearson coefficient r = 0.59) between the degree of benefit reported via the patient survey and the degree of benefit reported via the Glasgow Benefit Inventory. A moderate correlation (Pearson coefficient r = 0.66) was observed between speech comprehension scores in quiet for the preoperative unaided condition and the postoperative aided Vibrant Soundbridge condition. No correlation was observed between subjective reports of satisfaction postoperatively and performance on preoperative objective tests or patient characteristics. Conclusion The results indicate a high level of satisfaction with the VSB as a treatment of sensorineural hearing impairment in patients with a wide range of characteristics. Preoperative scores for unaided speech comprehension tests in quiet may be a potential indicator of success on aided Vibrant Soundbridge speech comprehension tests postoperatively but do not reflect patient satisfaction with the device reported on self-assessment scales.

Evidence of a medial olivocochlear involvement in contralateral suppression of otoacoustic emissions in humans

Otoacoustic emissions (OAEs) evoked by click stimuli were recorded in both ears of 20 normal human subjects, in the presence and absence of a contralateral masking broad band noise. No difference in the amplitude of OAE suppression was noted between the first tested ear and the second one. In addition, 20 pathological subjects were tested according to the same protocol. Ten of them belonged to a group of patients whose vestibular nerve was sectioned on one side to relieve incapacitating vertigo and thus represented a group in whom olivocochlear efferents were severed. A great reduction of suppression observed in the operated ear suggested that olivocochlear efferent fibers are necessary to obtain a full suppressive effect. Three of the pathological subjects were patients who had undergone a decompression of the facial nerve which necessitated the same surgical approach as vestibular neurotomy, but without any section of vestibular fibers. This surgical control group demonstrated that the surgical act by itself cannot explain the difference observed in the neurotomized group. Finally, seven of the pathological subjects were patients with Bells palsy, which paralyses the facial nerve and abolishes the stapedial reflex. No suppression difference was observed between healthy ears and ears without stapedial reflex. Therefore, it appeared that the stapedial reflex was not involved in the contralateral suppression of EOAEs. However, as the tensor tympani muscle remained functional in these patients, its involvement in the suppressive effect cannot be excluded.

Walking performance of vestibular-defective patients before and after unilateral vestibular neurotomy

The present study investigated goal-directed linear locomotion in nine Menières patients before and after (1 week, 1 and 3 months) a curative unilateral vestibular neurotomy (UVN). Experiments were done using a 3D motion analysis system in subjects walking eyes open (EO) and eyes closed (EC) towards a real or memorized target, respectively. Locomotor pattern (velocity, step length, step frequency and walk ratio) and walking trajectory deviations were evaluated for normal and fast speeds of locomotion and compared to those recorded in 10 healthy subjects. Before UVN, patients showed no walking deviation but gait pattern changes characterized by slower walks compared to the controls, mainly due to step length and step frequency reductions for both visual conditions and locomotion speeds. In the acute stage after UVN, locomotor pattern impairments were significantly accentuated. On the other hand, patients showed strong walking deviations towards the lesioned side with EC. Opposite lateral deviation towards the intact side were observed with EO for normal speed only. Recovery from impaired locomotor pattern was achieved within 1 month for normal speed but remained uncompensated 3 months post-lesion for fast speed particularly in EC condition. Finally, the walking trajectory deviation towards the lesioned side in the dark was maintained up to 3 months after UVN. The results show that central processing of visual and vestibular cues contributes to an accurate locomotor pointing. They argue for an increased weight of visual reference frame on locomotor functions when vestibular function is unilaterally impaired.

Retrosigmoid approach for small and medium-sized acoustic neuromas

Objective Clinical study of the keyhole acoustic neuroma retrosigmoid approach for facial nerve and hearing preservation. Study Design This was a prospective case review from October 1993 to December 1998 in a referral hospital care unit. Patients A total of 119 consecutive patients with a tumor size of <25 mm in the cerebellopontine angle corrected by a retrosigmoid approach were included in the study. Interventions Standard audiometric and imaging assessments, complete tumor removal by using endoscopy-assisted control, and nerve monitoring. Main Outcome Measures House-Brackmann facial nerve grade and hearing level by the American Academy of Otolaryngology–Head and Neck Surgery classification. Results Grades I and II facial nerve function was obtained in 96% of cases, measurable hearing was preserved in 49% of cases, and 30% of cases achieved serviceable hearing. Conclusion The retrosigmoid approach is a safe and reliable approach in random patients with small and medium-sized acoustic neuromas.

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.

How changes in vestibular and visual reference frames combine to modify body orientation in space.

The aim of this study was to analyse how changes in vestibular and visual reference frames combine to modify body orientation in space, and to determine the relationship between postural, oculomotor and perceptive parameters. Changes in vestibular and visual references were investigated by comparing controls and vestibular defective patients (Ménières patients tested before and one week after unilateral vestibular nerve section) under three visual contexts (light with and without vertical and horizontal coordinates, darkness). Unilateral vestibular loss was responsible for postural and perceptive deviations whose direction depended on the presence of visual reference frame. We suggest these changes vary according to the spatial reference frame patients are based on. Postural changes were related to perceptive modifications but not to eye cyclotorsion.

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.