Evelyne Ferrary

Cardiovascular and Thromboembolic Risk Factors in Idiopathic Sudden Sensorineural Hearing Loss: A Case-Control Study

Objective: The pathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL) remains unknown, but vascular involvement is one of the main hypotheses. The main objective of this study was to investigate the association between ISSHL and cardiovascular and thromboembolic risk factors. Study Design: Multicentric case-control study. Methods: Ninety-six Caucasian patients with ISSHL and 179 sex- and age-matched controls were included. Patients were evaluated on the day of the inclusion and 1 week, 3 weeks and 3 months later. Clinical information concerning personal and familial cardiovascular and thromboembolic risk factors and concerning the ISSHL was collected. Blood samples were collected for genetic analysis of factor V Leiden and G20210A polymorphism in the factor II gene. The severity of the hearing loss was classified as mild (21–40 dB), moderate (41–70 dB), severe (71–90 dB) and profound or total (>90 dB). Hearing improvement was calculated as a relative improvement of hearing thresholds using the contralateral ear as baseline. Results: Systolic blood pressure was higher in patients (130 ± 1.7 mm Hg) than in controls (124 ± 1.1 mm Hg, p = 0.003). The personal/familial history of cardiovascular events was also more prevalent in patients (p = 0.023 and p = 0.014, respectively), whereas no difference was found in the prevalence of personal cardiovascular risk factors (hypertension, diabetes mellitus, hyperlipidemia, smoking habits). There was no correlation between the audiogram type, the hearing outcome and the presence of cardiovascular risk factors. No significant difference was observed in the personal/familial history or in the presence of thromboembolic risk factors. The prothrombin and factor V mutations were uncommon in both patients and controls. The final hearing threshold was only correlated with the severity of the initial hearing loss (p < 0.001), but not influenced by the presence of vertigo, audiogram type, time elapsed from onset of ISSHL to hospitalization or failure of a previous oral therapy. Hearing stabilization was obtained at 21 days in 92% of patients. Conclusion: These results support the theory of vascular involvement as the etiology of some cases of ISSHL. The sole predictive factor of poor final hearing is the severity of the initial hearing loss.

Prostaglandin synthesis by the cochlea of the guinea pig. Influence of aspirin, gentamicin, and acoustic stimulation

This study describes the synthesis of prostaglandins (PGs) by the vascular structures of the inner ear (lateral wall = stria vascularis and spiral ligament) in vitro. The main PGs produced were PGI2, PGF2 alpha and PGE2. PGI2 and PGF2 alpha were also found in the perilymph. A 350 mg/kg ip injection of aspirin decreased PG synthesis by the lateral wall and PG levels in perilymph. This effect was reversed after 3 days. Gentamicin (10(-9) to 10(-5) M) decreased significantly and reversibly PG synthesis in vitro, as did 100 mg/kg ip injection. Acoustic stimulation increased ex vivo PGI2 and PGE2 synthesis without modifying PG levels in perilymph. Results suggest that PGs could be one humoral mediator of the cochlear microcirculation homeostasis, and, possibly, of the circulatory disturbances reported after acoustic stimulation. The decreased PG synthesis after gentamicin treatment could account for the angiotoxic component observed in aminoglycoside ototoxicity.

Speech Performance and Sound Localization in a Complex Noisy Environment in Bilaterally Implanted Adult Patients

Objective: To evaluate speech performance, in quiet and noise, and localization ability in adult patients who had undergone bilateral and simultaneous implantation. Study Design: Prospective multi-center study. Methods: Twenty-seven adult patients with profound or total hearing loss were bilaterally implanted in a single-stage procedure, and simultaneously activated (Med-El, Combi 40/40+). Subjects were assessed before implantation and at 3, 6 and 12 months after switch-on. Speech perception tests in monaural and binaural conditions were performed in quiet and in noise using disyllabic words, with speech coming from the front and a cocktail party background noise coming from 5 loudspeakers. Sound localization measurements were also performed in background noise coming from 5 loudspeakers positioned from –90° to +90° azimuth in the horizontal plane, and using a speech stimulus. Results: There was a bilateral advantage at 12 months in quiet (77 ± 5.0% in bilateral condition, 67 ± 5.3% for the better ear, p < 0.005) and in noise (signal-to-noise ratio +15 dB: 63 ± 5.9% in bilateral condition, 55 ± 6.9% for the better ear, p < 0.05). Considering unilateral speech scores recorded in quiet at 12 months, subjects were categorized as ‘good performers’ (speech comprehension score ≥60% for the better ear, n = 19) and ‘poor performers’ (n = 8). Subjects were also categorized as ‘asymmetrical’ (difference between their 2 unilateral speech scores ≥20%, n = 11) or ‘symmetrical’ (n = 16). The largest advantage (bilateral compared to the better ear) was obtained in poor performers: +19% compared to +7% in good performers (p < 0.05). In the group of good performers, there was a bilateral advantage only in cases of symmetrical results between the 2 ears (n = 10). In the group of poor performers, the bilateral advantage was shown in both patients with symmetrical (n = 6) and asymmetrical results (n = 2). In bilateral conditions, the sound localization ability in noise was improved compared to monaural conditions in patients with symmetrical and asymmetrical performance between the 2 ears. No preoperative factor (age, duration of deafness, use of hearing aids, etiology, etc.) could predict the asymmetrical performance, nor which ear would be the best. Conclusion: This study demonstrates a bilateral advantage (at 12 months after the implantation) in speech intelligibility and sound localization in a complex noisy environment. In quiet, this bilateral advantage is shown in cases of poor performance of both ears, and in cases of good performance with symmetrical results between the 2 ears. No preoperative factor can predict the best candidates for a simultaneous bilateral implantation.

Production of endolymph in the semicircular canal of the frog Rana esculenta.

The mechanisms of secretion of endolymph were studied in vitro in the isolated inner ear of the frog. Prior to in vitro experiments, the composition of perilymph was evaluated in vivo and compared to that of plasma. Composition of perilymph resembled that of an extracellular fluid, although Na and Cl concentrations were higher and K concentration was lower in perilymph than in plasma water. No difference in Ca and Mg concentrations was observed between these two fluids. Osmolality averaged 227 mosmol/kg H2O in perilymph and 183 mosmol/kg H2O in plasma. Endolymph in frog inner ear corresponded in chemical pattern to mammalian endolymph. K and Na concentrations in endolymph collected from the ampulla of the posterior vertical semicircular canal averaged 121.1 mM and 2.5 mM, respectively. Osmolality of endolymph was 237 mosmol/kg H2O. K and Na concentrations were unaltered when inner ears were incubated for 24 h either at 15 degrees C or at 4 degrees C. Addition of ouabain (10(‐4) M) to the perilymph‐like bathing solution altered greatly Na and K composition of endolymph after incubation for 3 h at 15 degrees C. The Na and K concentration gradients between endolymph and the bath were abolished after incubation for 24 h. Ligatures of the posterior vertical semicircular canal were performed at different sites to isolate some parts of the canal, i.e. the ampulla and the non‐ampullar duct. K concentration in the ampulla after incubation for 24 h remained as high as 20 times that in the bath. This K gradient was abolished in the presence of ouabain (10(‐4) M). High K concentration could be maintained in the non‐ampullar part of the semicircular canal only if the latter communicated with the ampulla. It is concluded that endolymph is actively secreted into the ampulla of the semicircular canal. Na+‐K+‐activated ATPase in the ampullar dark cells may energize the ouabain sensitive ionic transports that are involved in the production of endolymph. Endolymph secreted into the ampulla would spread intraluminally to account for the high K and low Na concentrations of the fluid which fills the non‐secretory part of the semicircular canal.

Plastin 1 Binds to Keratin and Is Required for Terminal Web Assembly in the Intestinal Epithelium

Plastin 1 (I-plastin, fimbrin) along with villin and espin is a prominent actin-bundling protein of the intestinal brush border microvilli. We demonstrate here that plastin 1 accumulates in the terminal web and interacts with keratin 19, possibly contributing to anchoring the rootlets to the keratin network. This prompted us to investigate the importance of plastin 1 in brush border assembly. Although in vivo neither villin nor espin is required for brush border structure, plastin 1-deficient mice have conspicuous ultrastructural alterations: microvilli are shorter and constricted at their base, and, strikingly, their core actin bundles lack true rootlets. The composition of the microvilli themselves is apparently normal, whereas that of the terminal web is profoundly altered. Although the plastin 1 knockout mice do not show any overt gross phenotype and present a normal intestinal microanatomy, the alterations result in increased fragility of the epithelium. This is seen as an increased sensitivity of the brush border to biochemical manipulations, decreased transepithelial resistance, and increased sensitivity to dextran sodium sulfate-induced colitis. Plastin 1 thus emerges as an important regulator of brush border morphology and stability through a novel role in the organization of the terminal web, possibly by connecting actin filaments to the underlying intermediate filament network.

Conservative management versus surgery for small vestibular schwannomas

Conclusion A high rate of deterioration in hearing function and the loss of patient compliance during conservative management should be taken into account when considering hearing preservation strategies for patients with vestibular schwannoma (VS). Objective To compare conservative management with surgery for solitary small VS. Material and methods Among 693 patients followed up for VS between 1991 and 2002, 114 (16%) intracanalicular VSs (stage 1) and 302 (44%) VSs measuring <15 mm in the cerebellopontine angle (stage 2) were included in this study. Initially, surgery was performed in 305 (73%) cases (50 stage 1, 255 stage 2) and 111 (27%) were managed conservatively (64 stage 1, 54 stage 2) by means of annual MRI scans and audiometry. Conservative management was chosen in patients aged >60 years and in those who refused surgery. In this subgroup, the mean follow-up period was 33 months (range 6–111 months). Results In the conservative management group, 47% of VSs showed significant growth, 47% were stable and 6% showed regression. Seventeen patients (15%) were operated on secondarily for tumour growth and 1 (1%) was irradiated for tumour growth and because surgery was contraindicated. Deterioration of hearing function by ≥1 class was observed in 56% of cases, 34% of patients were initially in hearing class D and only 10% showed stable hearing function. Of the conservative management group, 17% were lost during follow-up. After surgery, grade 1 or 2 facial function was obtained in 86% of cases. Following hearing preservation attempts (n=137), 54% of patients were in hearing classes A–C.

Recent advances in local drug delivery to the inner ear

Inner ear diseases are not adequately treated by systemic drug administration mainly because of the blood-perilymph barrier that reduces exchanges between plasma and inner ear fluids. Local drug delivery methods including intratympanic and intracochlear administrations are currently developed to treat inner ear disorders more efficiently. Intratympanic administration is minimally invasive but relies on diffusion through middle ear barriers for drug entry into the cochlea, whereas intracochlear administration offers direct access to the colchlea but is rather invasive. A wide range of drug delivery systems or devices were evaluated in research and clinic over the last decade for inner ear applications. In this review, different strategies including medical devices, hydrogels and nanoparticulate systems for intratympanic administration, and cochlear implant coating or advanced medical devices for intracoclear administration were explored with special attention to in vivo studies. This review highlights the promising systems for future clinical applications as well as the current hurdles that remain to be overcome for efficient inner ear therapy.

Cochlear Implant Benefits in Deafness Rehabilitation: PET Study of Temporal Voice Activations

Cochlear implants may improve the medical and social prognosis of profound deafness. Nevertheless, some patients have experienced poor results without any clear explanations. One correlate may be an alteration in cortical voice processing. To test this hypothesis, we studied the activation of human temporal voice areas (TVA) using a well-standardized PET paradigm adapted from previous functional MRI (fMRI) studies. Methods: A PET H215O activation study was performed on 3 groups of adult volunteers: normal-hearing control subjects (n = 6) and cochlear-implanted postlingually deaf patients with >2 y of cochlear implant experience, with intelligibility scores in the “Lafon monosyllabic task” >80% (GOOD group; n = 6) or <20% (POOR group; n = 6). Relative cerebral blood flow was measured in 3 conditions: rest, passive listening to human voice, and nonvoice stimuli. Results: Compared with silence, the activations induced by nonvoice stimuli were bilaterally located in the superior temporal regions in all groups. However these activations were significantly and similarly reduced in both cochlear implant groups, whereas control subjects showed supplementary activations. Compared with nonvoice, the voice stimuli induced bilateral activation of the TVA along the superior temporal sulcus (STS) in both the control and the GOOD groups. In contrast, these activations were not detected in the POOR group, which showed only left unilateral middle STS activation. Conclusion: These results suggest that PET is an adequate method to explore cochlear implant benefits and that this benefit could be linked to the activation of the TVA.

Local administration of antioxidants to the inner ear: Kinetics and distribution

Round window (r.w.) administration of drugs involves the delivery of medication directly into the inner ear via the r.w. membrane, avoiding a systemic effect of the therapy. Earlier experimental studies suggest that a number of antioxidants and scavengers hold promise for ameliorating the tissue damaging capacity of reactive oxygen species in some acquired cochlear disorders. D-Methionine and thiourea are two small sulfur-containing molecules with an antioxidative and scavenging effect. The passage through the r.w. of radioactive D-methionine and thiourea administered by 1 h infusion to the r.w. was studied in a rat model. Levels of the tracers were measured in scala tympani perilymph (PLT) 17-254 min after r.w. administration. Both tracers pass the r.w. membrane readily. Peak levels were found in the earliest taken samples after the administration. The radioactivity in PLT of the basal turn reached a peak to about 1.5-1.9% of the irrigating medium radioactivity. Following the r.w. administration, the concentration of radioactive D-methionine and thiourea declined with a terminal half-life of 0.57 and 0.77 h, respectively. The distribution of the tracers at the cellular level was analyzed by autoradiography. The most intense expression was found in the lateral wall of the cochlea. It can be postulated that local delivery to the cochlea of D-methionine and thiourea via the r.w. gives high local concentrations of the substances in PLT in the basal turn.

Friction force measurement during cochlear implant insertion: application to a force-controlled insertion tool design

Hypothesis The aim of the study was to evaluate force profiles during array insertion in human cochlea specimens and to evaluate a mechatronic inserter using a 1-axis force sensor. Background Today, the surgical challenge in cochlear implantation is the preservation of the anatomic structures and the residual hearing. In routine practice, the electrode array is inserted manually with a limited sensitive feedback. Materials and Methods Hifocus 1J electrode arrays were studied. The bench test comprised a mechatronic inserter combined to a 1-axis force sensor between the inserter and the base of the array and a 6-axis force sensor beneath the cochlea model. Influence of insertion tube material, speed (0.15, 0.5, and 1.5 mm/s) and lubricant on frictions forces were studied (no-load). Different models were subsequently evaluated: epoxy scala tympani model and temporal bones. Results Frictions forces were lower in the plastic tube compared with those in the metal tube (0.09 ± 0.028 versus 0.14 ± 0.034 at 0.5 mm/s, p < 0.001) and with the use of hyaluronic acid gel. Speed did not influence frictions forces in our study. Insertion force profiles provided by the 1- and 6-axis force sensors were similar when friction forces inside the insertion tool (no-load measurements) were subtracted from the 1-axis sensor data in the epoxy and temporal bone models (mean error, 0.01 ± 0.001 N). Conclusion Using a sensor included in the inserter, we were able to measure array insertion forces. This tool can be potentially used to provide real-time information to the surgeon during the procedure.