Alexander M. Huber

Grafts of adenosine-releasing cells suppress seizures in kindling epilepsy

Adenosine is an inhibitor of neuronal activity in the brain. The local release of adenosine from grafted cells was evaluated as an ex vivo gene therapy approach to suppress synchronous discharges and epileptic seizures. Fibroblasts were engineered to release adenosine by inactivating the adenosine-metabolizing enzymes adenosine kinase and adenosine deaminase. After encapsulation into semipermeable polymers, the cells were grafted into the brain ventricles of electrically kindled rats, a model of partial epilepsy. Grafted rats provided a nearly complete protection from behavioral seizures and a near-complete suppression of afterdischarges in electroencephalogram recordings, whereas the full tonic–clonic convulsions in control rats remained unaltered. Thus, the local release of adenosine resulting in adenosine concentrations <25 nM at the site of action is sufficient to suppress seizure activity and, therefore, provides a potential therapeutic principle for the treatment of drug-resistant partial epilepsies.

Factors Affecting Auditory Performance of Postlinguistically Deaf Adults Using Cochlear Implants: An Update with 2251 Patients

Objective: To update a 15-year-old study of 800 postlinguistically deaf adult patients showing how duration of severe to profound hearing loss, age at cochlear implantation (CI), age at onset of severe to profound hearing loss, etiology and CI experience affected CI outcome. Study Design: Retrospective multicenter study. Methods: Data from 2251 adult patients implanted since 2003 in 15 international centers were collected and speech scores in quiet were converted to percentile ranks to remove differences between centers. Results: The negative effect of long duration of severe to profound hearing loss was less important in the new data than in 1996; the effects of age at CI and age at onset of severe to profound hearing loss were delayed until older ages; etiology had a smaller effect, and the effect of CI experience was greater with a steeper learning curve. Patients with longer durations of severe to profound hearing loss were less likely to improve with CI experience than patients with shorter duration of severe to profound hearing loss. Conclusions: The factors that were relevant in 1996 were still relevant in 2011, although their relative importance had changed. Relaxed patient selection criteria, improved clinical management of hearing loss, modifications of surgical practice, and improved devices may explain the differences.

Pre-, Per- and Postoperative Factors Affecting Performance of Postlinguistically Deaf Adults Using Cochlear Implants: A New Conceptual Model over Time

Objective To test the influence of multiple factors on cochlear implant (CI) speech performance in quiet and in noise for postlinguistically deaf adults, and to design a model of predicted auditory performance with a CI as a function of the significant factors. Study Design Retrospective multi-centre study. Methods Data from 2251 patients implanted since 2003 in 15 international centres were collected. Speech scores in quiet and in noise were converted into percentile ranks to remove differences between centres. The influence of 15 pre-, per- and postoperative factors, such as the duration of moderate hearing loss (mHL), the surgical approach (cochleostomy or round window approach), the angle of insertion, the percentage of active electrodes, and the brand of device were tested. The usual factors, duration of profound HL (pHL), age, etiology, duration of CI experience, that are already known to have an influence, were included in the statistical analyses. Results The significant factors were: the pure tone average threshold of the better ear, the brand of device, the percentage of active electrodes, the use of hearing aids (HAs) during the period of pHL, and the duration of mHL. Conclusions A new model was designed showing a decrease of performance that started during the period of mHL, and became faster during the period of pHL. The use of bilateral HAs slowed down the related central reorganization that is the likely cause of the decreased performance.

Evaluation of Eardrum Laser Doppler Interferometry as a Diagnostic Tool

Objectives Laser Doppler interferometry (LDI) of the eardrum allows noncontact optical analysis of its vibrations in response to sound. Although LDI has been widely used in research, it has not yet been introduced into clinical practice as an adjunctive test for otological workup. The aim of this study was to evaluate LDI as a diagnostic tool in the clinical sphere.

Intraoperative assessment of stapes movement.

A method is described that allows, for the first time, intraoperative vibration modes assessment of the acoustically stimulated stapes by means of scanning laser Doppler interferometry (LDI). The study was designed to answer the following questions: 1) Is LDI practical for taking measurements during surgery? 2) Are the results comparable to the findings in temporal bone preparations? and 3) Do the vibration characteristics of the stapes change after the posterior incudal ligament is detached from the incus? Seven patients with profound bilateral hearing loss who were undergoing cochlear implantation were included in the study. The measurement system was easily applicable for intraoperative measurements and allowed contact-free analysis with very high accuracy. No major differences in the results from the live human subjects and temporal bone preparations were observed. The stapes movement was predominantly pistonlike at the lower frequencies and became complex at higher frequencies. Sacrificing the posterior incudal ligament had no statistically significant effect on stapes vibration.

Frey's Syndrome After Parotidectomy: A Retrospective and Prospective Analysis

Gustatory sweating is a well‐known sequela after parotid surgery. In a retrospective and prospective study of patients undergoing parotid surgery, the onset, time course, extent, and treatment modalities of Freys syndrome were analyzed. Twenty‐two percent of the patients evaluated by questionnaires and 43% of the patients followed prospectively within 1 year were found to be symptomatic. Although the Minor starch‐iodine test was positive in 38% of patients at 3 months, none of these patients experienced symptoms. Up to 12 months after surgery the rate of patients who tested positive increased to 96% and the total area of sweating expanded to a mean value of 18 cm2. Whereas most of the patients are not markedly disturbed, few patients (5% to 10%) suffer from severe gustatory sweating. These patients present a therapeutic challenge.

The incudo-malleolar joint and sound transmission losses.

The question as to whether the incudo-malleolar joint (IMJ) is mobile or immobile at moderate sound pressure levels (SPLs) is addressed. Referring to the mechanical properties of elastic tissue, we suggest that the IMJ is mobile at any SPL. In order to test this hypothesis, we investigated the dynamics of the IMJ in nine temporal bones by means of laser scanning doppler vibrometry. The dynamic behavior of both ossicles, malleus and incus is described by three degrees of freedom, and transfer functions (TFs) are shown for each motion component [corrected]. We show that there is indeed relative motion between the malleus and the incus. This transmission loss affects the middle ear TF and results in a frequency dependent sound transmission loss. Some characteristics of our results are in agreement with middle ear TFs described in the literature. The increasing transmission loss towards higher frequencies is caused by relative motion between malleus and incus at the IMJ. The concept that the IMJ is functionally mobile is consistent with the physical properties of elastic tissues which most likely define the mechanics of this joint. Since the IMJ is indeed mobile at moderate sound intensities and audible frequencies the theory of the lever ratio being responsible for the characteristics of the middle ear TF must be reconsidered.

Subjective and objective results after bilateral cochlear implantation in adults.

Objective: To assess and compare subjective and objective results after bilateral cochlear implantation with a special emphasis on time interval between the first and second implant. Study Design: Clinical trial. Setting: Tertiary referral center. Patients: All consecutively bilaterally implanted adult patients who had used the second implant for more than 6 months were selected for the study. They had to have the mental capacity to answer questions regarding their hearing abilities and fill out a questionnaire (n = 34). Twenty-nine patients (85%) finally could be included in the study (age at first implantation, 31.0 ± 16 yr [mean ± standard deviation {SD}], time to second implantation, 5.6 ± 5.7 yr [mean ± SD]). In all patients, a full insertion (21 electrodes) of the implant was achieved. For the subjective part of the study, the patients were matched with unilaterally implanted subjects selected according to specified criteria. Interventions: Sequential or simultaneous cochlear implantation with a Nucleus device. Main Outcome Measures: Speech comprehension measures were performed using the Oldenburger sentences in quiet and in noise with unilateral and bilateral implant use. Summation effect, head shadow effect, squelch effect, and interaural difference in quiet and noise were calculated. Advantage for binaural stimulation with respect to the unilateral condition was assessed for each individual. Additionally, a localization test was performed using 12 speakers arranged in a circle. Subjective benefit was assessed by a questionnaire (The Speech, Spatial and Qualities of Hearing Scale). Results were analyzed with special emphasis on effects of timing and intervals. Results: There was a statistically significant advantage for the head shadow effect test (p < 0.05) when the sound source was located on the activated side. There was also a statistically significant correlation of the subjective and objective results and a strong correlation of the interaural difference of speech intelligibility in quiet and the time interval between the first and the second implant (p < 0.001; r2 = 55%). In the bi-implanted state, an interaural difference of 18 ± 27% and 3 ± 2.2 dB signal-to-noise ratio (mean ± SD) was measured in quiet and noise, respectively. The mean results for the bilateral condition for the summation effect, the squelch effect, and speech discrimination in quiet were better than in the unilateral condition but were not statistically significant. The subjective results of the bilateral group were better in all categories than the results of the unilateral group but were just below statistical significance. Conclusion: Speech understanding in noise is improved with bilateral cochlear implantation with unambiguous evidence that the second implant expands the sound field for effective speech recognition. Communication in daily life is facilitated, as determined by the subjective Speech, Spatial and Qualities of Hearing Scale test. The correlation of the subjective and objective results confirms the practical benefits in daily activities. Although there was improvement with a second Cochlear implant even after a long implantation interval, short intervals lead to better results.

Stapes Prosthesis Attachment: The Effect of Crimping on Sound Transfer in Otosclerosis Surgery

Objectives/Hypothesis Although in stapes surgery successful hearing improvement may be achieved in the majority of patients, unsatisfactory closure of the air–bone gap can be recorded. One of many reasons for unexpected failures of stapes surgery may be the insufficient crimping of a stapes prosthesis onto the incus. The objectives of the study were to assess the amount of sound transmission loss in response to the quality of prosthesis crimping and to identify a required loop attachment pattern to obtain good sound transmission results.

Fixation of the anterior mallear ligament : diagnosis and consequences for hearing results in stapes surgery

In the search for possible causes of unfavorable results after stapes surgery, the study reported here focused on the anterior mallear ligament, since it has been previously reported that partial mallear fixation (PMF) leads to functional failure in 38% of cases of stapes revision surgery. The aims of the study were to identify effective methods for the diagnosis of PMF and experimentally assess the conductive hearing loss that results from PMF. The study included vibration amplitude measurements of the ossicles by laser Doppler interferometry (LDI) in 19 patients and 5 fresh human temporal bone (TB) specimens. Analysis of their dynamic behavior was performed by finite element modeling (FEM). Similar, significant changes of manubrium vibration patterns for PMF were found by FEM calculations, in TB experiments, and in patients. We could identify PMF either before operation, using LDI, or during operation, by manual palpation. In the TB experiments and FEM calculations, the attenuation of the stapes displacement due to an isolated PMF was approximately 10 dB and frequency-dependent. Untreated anterior mallear ligament fixation produced a persistent air-bone gap of approximately 10 dB after stapedioplasty.