Innovative 3D Model of the Human Middle Ear in High Resolution with a Histological Microgrinding Method: A Feasibility Study and Comparison with μCT

Conclusion. The development of a histological 3D model of the tympanic cavity visualizes the exact microanatomy of the sound conduction organ and is therefore essential for finite elements simulations and surgical training. Objectives. So far, no accurate histological 3D model of the sound conduction system existed in literature. For 3D reconstruction of the very fine structures inside and outside the auditory ossicles, a method based on histological slices allows a more differential analysis of both hard and soft tissues and could thus be superior to μCT. Method. A complete temporal bone was embedded in epoxy resin and microground in distances of about 34 μm. After photodocumentation of every plane, a 3D reconstruction was performed by using the Computer Aided Design (CAD) program Rhinoceros 5®. For comparison, a μCT of the same specimen resulted in a 3D model of the calcified structures in the middle ear. Results. The histological 3D model gives an excellent overview to all anatomical soft and bony tissues of the human auditory ossicles. Specifically the fine blood vessel system and the exact dimension of cartilage areas inside the ossicles can be illustrated much more precisely than with μCT data. The present technique also allows the evaluation of the fine connecting ligaments inside the tympanic cavity

Middle ear anatomy and implant sizes: correlates and the need for uniform implant dimensions

IntroductionConductive hearing loss describes an insufficient sound transfer of the middle ear, often caused by defects or absence of the ossicles. Depending on the specific middle ear dimensions and the kind of defect, surgeons can choose from a variety of passive implants to reconstruct the middle ear and hence restore sound transmission. However, the latter is only achieved if the optimal implant size is available and selected for each individual patient.MethodsAnatomical dimensions relevant for middle ear reconstruction were assessed within high-resolution clinical imaging data of 50 patients (100 ears). The ranges of these dimensions were then compared to implant types and sizes available from different manufacturers.ResultsIn general, total and partial prostheses seem to cover the whole range of anatomical variations. A lack of stapesplasty implants was found for particularly small anatomies. Various implant lengths of all types far exceed dimensions necessary for successful restoration of sound transmission. In some cases, implant lengths are not clearly specified by the manufacturer. Tympanic membrane and stapes axis were not in line for any of the investigated middle ears.ConclusionClear specifications of implant lengths are crucial to allow for successful hearing restoration, and clinics often need to have more than one implant type to cover the entire range of anatomical variations they may encounter. There appears to be an unmet clinical need for smaller stapesplasty implants. Devices which allow for an angular adjustment between distal and proximal end appear to mimic the orientation of the ossicles more naturally

Evaluating a Novel Class of Biomaterials: Magnesium-Containing Layered Double Hydroxides

Metallic magnesium and compounds such as magnesium hydroxide Mg(OH)2 have been shown to have osteoconductive properties under experimental conditions and are gaining an increasing interest in the field of degradable biomaterials. The application of the compounds as implant coatings could support implant incorporation, resulting in an increased period of use of the implants. A variety of Mg-containing Layered Double Hydroxides (Mg-LDHs) has been synthesized and examined. These materials have been tested in various in vitro and in vivo studies; the latter took place in different sites like in the middle ear or in the condyle of New Zealand White Rabbits. In the latest study newly formed bone could be found around the Mg-Al-CO3-LDH pellets, making it a promising compound for bone-healing applications.DFG/SFB/59

Detection of BDNF-Related Proteins in Human Perilymph in Patients With Hearing Loss

The outcome of cochlear implantation depends on multiple variables including the underlying health of the cochlea. Brain derived neurotrophic factor (BDNF) has been shown to support spiral ganglion neurons and to improve implant function in animal models. Whether endogenous BDNF or BDNF-regulated proteins can be used as biomarkers to predict cochlear health and implant outcome has not been investigated yet. Gene expression of BDNF and downstream signaling molecules were identified in tissue of human cochleae obtained from normal hearing patients (n = 3) during skull base surgeries. Based on the gene expression data, bioinformatic analysis was utilized to predict the regulation of proteins by BDNF. The presence of proteins corresponding to these genes was investigated in perilymph (n = 41) obtained from hearing-impaired patients (n = 38) during cochlear implantation or skull base surgery for removal of vestibular schwannoma by nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC-MS/MS). Analyzed by mass spectrometry were 41 perilymph samples despite three patients undergoing bilateral cochlear implantation. These particular BDNF regulated proteins were not detectable in any of the perilymph samples. Subsequently, targeted analysis of the perilymph proteome data with Ingenuity Pathway Analysis (IPA) identified further proteins in human perilymph that could be regulated by BDNF. These BDNF regulated proteins were correlated to the presence of residual hearing (RH) prior to implantation and to the performance data with the cochlear implant after 1 year. There was overall a decreased level of expression of BDNF-regulated proteins in profoundly hearing-impaired patients compared to patients with some RH. Phospholipid transfer protein was positively correlated to the preoperative hearing level of the patients. Our data show that combination of gene expression arrays and bioinformatic analysis can aid in the prediction of downstream signaling proteins related to the BDNF pathway. Proteomic analysis of perilymph may help to identify the presence or absence of these molecules in the diseased organ. The impact of such prediction algorithms on diagnosis and treatment needs to be established in further studies

Redesign of the Hannover Coupler: Optimized Vibration Transfer from Floating Mass Transducer to Round Window

Introduction. In order to reduce the large variations in clinical outcomes of patients with implanted MED-EL Floating Mass Transducer (FMT) at the round window (RW), several approaches were proposed to optimize FMT-RW coupling. Our previous study showed improved FMT-RW coupling by applying static RW loads utilizing the “Hannover Coupler” (HC) FMT-prosthesis but also demonstrated insufficient low frequency performance. Hence, a redesigned HC version (HCv2) was investigated in this study. Methods. Experiments were performed in ASTM F2504-05 compliant fresh human temporal bones. The HCv2 is a FMT-prosthesis redesigned from a previous prototype to specifically improve low frequency performance. Stapes footplate (SFP) displacements in response to acoustic stimulation of the tympanic membrane and to FMT-RW stimulation at varying static force (0–100 mN) were measured by Laser-Doppler vibrometry. Results. SFP displacements were highly dependent on the applied RW load and had a global maximum at 15 mN when averaged at speech relevant frequencies (0.5–4 kHz). SFP responses at frequencies ≤ 1 kHz were up to 25 dB higher than responses achieved with the previous HC version. Conclusion. Optimizing the HC prosthesis design resulted in improved SFP responses to RW stimulation especially at lower frequencies (≤1 kHz)

Proteome profile of patients with excellent and poor speech intelligibility after cochlear implantation: Can perilymph proteins predict performance?

Modern proteomic analysis and reliable surgical access to gain liquid inner ear biopsies have enabled in depth molecular characterization of the cochlea microenvironment. In order to clarify whether the protein composition of the perilymph can provide new insights into individual hearing performance after cochlear implantation (CI), computational analysis in correlation to clinical performance after CI were performed based on the proteome profile derived from perilymph samples (liquid biopsies). Perilymph samples from cochlear implant recipients have been analyzed by mass spectrometry (MS). The proteins were identified using the shot-gun proteomics method and quantified and analyzed using Max Quant, Perseus and IPA software. A total of 75 perilymph samples from 68 (adults and children) patients were included in the analysis. Speech perception data one year after implantation were available for 45 patients and these were used for subsequent analysis. According to their hearing performance, patients with excellent (n = 22) and poor (n = 14) performance one year after CI were identified and used for further analysis. The protein composition and statistically significant differences in the two groups were detected by relative quantification of the perilymph proteins. With this procedure, a selection of 287 proteins were identified in at least eight samples in both groups. In the perilymph of the patients with excellent and poor performance, five and six significantly elevated proteins were identified respectively. These proteins seem to be involved in different immunological processes in excellent and poor performer. Further analysis on the role of specific proteins as predictors for poor or excellent performance among CI recipients are mandatory. Combinatory analysis of molecular inner ear profiles and clinical performance data using bioinformatics analysis may open up new possibilities for patient stratification. The impact of such prediction algorithms on diagnosis and treatment needs to be established in further studies

Cochlear Implantation in Obliterated Cochlea: A Retrospective Analysis and Comparison between the IES Stiff Custom-Made Device and the Split-Array and Regular Electrodes

Anatomical malformations, obliterations of the cochlea, or re-implantations pose particular challenges in cochlear implantation. Treatment methods rely on radiological and intraoperative findings and include incomplete insertion, the implantation of a double array, and radical cochleostomy. In addition, a stiff electrode array, e.g., the IE stiff (IES) custom-made device (CMD, MED-EL), was prescribed individually for those special cases and pre-inserted prior to facilitate cochlear implantation in challenging cases. Data on outcomes after implantation in obliterated cochleae are usually based on individual case reports since standardised procedures are lacking. A retrospective analysis was conducted to analyse our cases on obliterated cochleae treated with MED-EL devices in order to allow the different cases to be compared. Impedances and speech perception data of patients treated with the IES CMD and the double array were retrospectively compared to patients treated with a STANDARD or FLEX electrode array (the REGULAR group). Patients with a Split-Array CMD had a poor speech perception when compared to patients treated with the IES CMD device. Thus, the IES CMD can successfully be used in patients with obliterated cochleae who would otherwise be non-users, candidates for a Split-Array CMD, or candidates for partial insertion with insufficient cochlear coverage

Trigeminal Nerve Affection in Patients with Neuro-Sjögren Detected by Corneal Confocal Microscopy

Background: Patients with Sjögren’s syndrome and polyneuropathy more frequently develop cranial nerve affection when compared to patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We therefore aimed to analyze trigeminal corneal nerve fibre characteristics in both patient groups. Methods: A total of 26 patients with Sjögren’s syndrome associated neuropathy and 29 patients with CIDP were recruited at our university hospital and compared to 6 healthy controls. Dry eye symptoms and signs were assessed via clinical examination and the Ocular Disease Surface Index questionnaire. Trigeminal corneal nerve fibres were analyzed via corneal confocal microscopy (CCM) as a non-invasive in vivo microscopy. Results: CCM revealed significantly reduced corneal nerve fibre density and corneal nerve fibre main branch density in the Neuro-Sjögren group when compared with healthy controls. There were no significant group differences between the Neuro-Sjögren and the CIDP group for any of the microscopic parameters. Dry eye assessment showed similarly reduced scores for both patient groups, while healthy controls showed better results for objective dry eye signs. There was no correlation between microscopic parameters of the corneal confocal microscopy and parameters of dry eye assessment. Conclusions: Our data revealed trigeminal corneal nerve affection in patients with neuropathy associated with Sjögren’s syndrome and patients with CIDP detected by CCM. No difference was found between both neuropathy groups indicating that CCM is not able to distinguish between both entities