Monitoring Cochlear Health With Intracochlear Electrocochleography During Cochlear Implantation: Findings From an International Clinical Investigation.

OBJECTIVES: Electrocochleography (ECochG) is emerging as a tool for monitoring cochlear function during cochlear implant (CI) surgery. ECochG may be recorded directly from electrodes on the implant array intraoperatively. For low-frequency stimulation, its amplitude tends to rise or may plateau as the electrode is inserted. The aim of this study was to explore whether compromise of the ECochG signal, defined as a fall in its amplitude of 30% or more during insertion, whether transient or permanent, is associated with poorer postoperative acoustic hearing, and to examine how preoperative hearing levels may influence the ability to record ECochG. The specific hypotheses tested were threefold: (a) deterioration in the pure-tone average of low-frequency hearing at the first postoperative follow-up interval (follow-up visit 1 [FUV1], 4 to 6 weeks) will be associated with compromise of the cochlear microphonic (CM) amplitude during electrode insertion (primary hypothesis); (b) an association is observed at the second postoperative follow-up interval (FUV2, 3 months) (secondary hypothesis 1); and (c) the CM response will be recorded earlier during electrode array insertion when the preoperative high-frequency hearing is better (secondary hypothesis 2). DESIGN: International, multi-site prospective, observational, between groups design, targeting 41 adult participants in each of two groups, (compromised CM versus preserved CM). Adult CI candidates who were scheduled to receive a Cochlear Nucleus CI with a Slim Straight or a Slim Modiolar electrode array and had a preoperative audiometric low-frequency average thresholds of ≤80 dB HL at 500, 750, and 1000 Hz in the ear to be implanted, were recruited from eight international implant sites. Pure tone audiometry was measured preoperatively and at postoperative visits (FUV1 and follow-up visit 2 [FUV2]). ECochG was measured during and immediately after the implantation of the array. RESULTS: From a total of 78 enrolled individuals (80 ears), 77 participants (79 ears) underwent surgery. Due to protocol deviations, 18 ears (23%) were excluded. Of the 61 ears with ECochG responses, amplitudes were < 1 µV throughout implantation for 18 ears (23%) and deemed "unclear" for classification. EcochG responses >1 µV in 43 ears (55%) were stable throughout implantation for 8 ears and compromised in 35 ears. For the primary endpoint at FUV1, 7/41 ears (17%) with preserved CM had a median hearing loss of 12.6 dB versus 34/41 ears (83%) with compromised CM and a median hearing loss of 26.9 dB ( p < 0.014). In assessing the practicalities of measuring intraoperative ECochG, the presence of a measurable CM (>1 µV) during implantation was dependent on preoperative, low-frequency thresholds, particularly at the stimulus frequency (0.5 kHz). High-frequency, preoperative thresholds were also associated with a measurable CM > 1 µV during surgery. CONCLUSIONS: Our data shows that CM drops occurring during electrode insertion were correlated with significantly poorer hearing preservation postoperatively compared to CMs that remained stable throughout the electrode insertion. The practicality of measuring ECochG in a large cohort is discussed, regarding the suggested optimal preoperative low-frequency hearing levels ( < 80 dB HL) considered necessary to obtain a CM signal >1 µV.

Further audiovestibular characterization of DFNB77, caused by deleterious variants in LOXHD1, and investigation into the involvement of Fuchs corneal dystrophy.

This study focuses on further characterization of the audiovestibular phenotype and on genotype-phenotype correlations of DFNB77, an autosomal recessive type of hearing impairment (HI). DFNB77 is associated with disease-causing variants in LOXHD1, and is genetically and phenotypically highly heterogeneous. Heterozygous deleterious missense variants in LOXHD1 have been associated with late-onset Fuchs corneal dystrophy (FCD). However, up to now screening for FCD of heterozygous carriers in DFNB77 families has not been reported. This study describes the genotype and audiovestibular phenotype of 9 families with DFNB77. In addition, carriers within the families were screened for FCD. Fifteen pathogenic missense and truncating variants were identified, of which 12 were novel. The hearing phenotype showed high inter- and intrafamilial variation in severity and progression. There was no evidence for involvement of the vestibular system. None of the carriers showed (pre-clinical) symptoms of FCD. Our findings expand the genotypic and phenotypic spectrum of DFNB77, but a clear correlation between the type or location of the variant and the severity or progression of HI could not be established. We hypothesize that environmental factors or genetic modifiers are responsible for phenotypic differences. No association was found between heterozygous LOXHD1 variants and the occurrence of FCD in carriers.

NF-κB signalling is involved in immune-modulation, but not basal functioning, of the mouse suprachiasmatic circadian clock.

Circadian rhythms are recurring near-24 hour patterns driven by an endogenous circadian timekeeping system. The master pacemaker in this system is the hypothalamic suprachiasmatic nucleus (SCN). Recently interest has been drawn to how the SCN clock responds to immune system stimulation. A major signalling component in the immune system is nuclear factor (NF)-κB. In the present study we examined the role of NF-κB in SCN function. Whilst serum shocked fibroblasts showed rhythmic nuclear localisation of p65 and p65-dependent transcription, there were no circadian changes in the SCN in expression of the NF-κB components p65, c-Rel, p-IκB or p-IKK. Chronic treatment with the NF-κB inhibitor PDTC did not impact on circadian or diurnal rhythms. Phase-shifting light pulses did not impact on SCN expression of p65, and PDTC treatment did not attenuate the behavioural or molecular response to light pulses. Peripheral treatment with lipopolysaccharide resulted in increased NF-κB component expression in the SCN. In vitro experiments with SCN slice cultures showed that treatment with NF-κB inhibitors did not markedly alter rhythmic changes in PER2::LUC expression. Further, SCN slices from nf-κb::luc mice did not show any evidence for circadian rhythms in NF-κB-mediated transcription. Experiments utilising older mice (~16 months old) showed that SCN treatment in vitro with PDTC resulted in increased amplitude of rhythmic PER2::LUC expression, and LPS treatment resulted in altered PER2::LUC rhythm acrophase. Overall, we interpret our results as providing evidence for the involvement of NF-κB in the suprachiasmatic circadian clock following immune stimulation, but not under basal conditions.

Discrimination of speech sound contrasts determined with behavioral tests and event-related potentials in cochlear implant recipients.

Cortical potentials evoked with speech stimuli were investigated in ten experienced cochlear implant (CI, type Nucleus 24M) users using three different speech-coding strategies and two different speech contrasts, one vowel (/i/-/a/) and one consonant (/ba/-/da/) contrast. On average, results showed that, compared to subjects with normal hearing, P300 amplitudes were smaller; however, most latencies were within the normal range. Next, individual P300 measures in response to the two speech contrasts were compared to behavioral discrimination scores. Significant within-subject differences in P300 amplitudes and latencies were found for the three speech coding strategies. These differences were in agreement with the behavioral, strategy-dependent discrimination of the speech contrasts.

Vestibular function and temporal bone imaging in DFNB1.

DFNB1 is the most prevalent type of hereditary hearing impairment known nowadays and the audiometric phenotype is very heterogeneous. There is, however, no consensus in literature on vestibular and imaging characteristics. Vestibular function and imaging results of 44 DFNB1 patients were evaluated in this retrospective study. All patients displayed a response during rotational velocity step testing. In 65% of the cases, the caloric results were within normal range bilaterally. The video head impulse test was normal in all patients. In 34.4% of the CT scans one or more temporal bone anomalies were found. The various anomalies found, were present in small numbers and none seemed convincingly linked to a specific DFNB1genotype. The group of DFNB1 patients presented here is the largest thus far evaluated for their vestibular function. From this study, it can be assumed that DFNB1 is not associated with vestibular dysfunction or specific temporal bone anomalies.

Quantitative diameter analysis of lingual nerve axons in man.

Previous studies on axon counts and fiber-diameter spectra in lingual nerves have been carried out only on animal models. This study reports an histological investigation on a series of 20 lingual nerves removed post mortem from human subjects. The results show wide variation in the myelinated fiber counts--a variation which does not appear to be related to the ages of the subjects. When the results are compared with those of a previous study (Heasman and Beynon, 1983), it is seen that the lingual nerve:inferior dental nerve ratio of axon counts is not a consistent index. The fiber-diameter spectrum for the human lingual nerve is characterized by a bimodal curve with the more pronounced peak in the small-diameter fiber range.

Myelinated fibre diameters of human inferior alveolar nerves.

These were examined in a series of 36 human post-mortem specimens. One unimodal, 32 bimodal and 1 trimodal diameter curves were demonstrated; group analysis of all samples gave a bimodal curve with 2-4 and 8-9 microns peaks.

A histochemical study on the distribution of melanin in human oral epithelium at six regional sites.

Oral mucosa from six sites in 95 autopsies was tested for melanin using the Masson-Fontana silver reduction method. Melanin was detected in 51.6% of labial, 46.3% of palatal, 45.3% of buccal, 28.4% of mandibular gingival, 25.3% of lingual and 21.1% of maxillary gingival samples. 93.7% of epidermal samples from the same population were positive. In 24.2% of the subjects there was no detectable melanin at any intraoral site and 4.2% showed activity in all six sites. The mean number of positive oral sites per individual was 2.2. There are thus regional differences in oral epithelial melanocyte activity, but no parallel with the known regional incidence of primary oral melanoma.

Preliminary quantitative microradiography study into the distribution of bone mineralization within the basal bone of the human edentulous mandible.

Six edentulous human hemimandibles (three male, three female) of similar ages were sectioned transversely at the midline, mental foramen, midway between mental foramen and angle (body), and angle of the mandible. Planoparallel sections were prepared of the cortical plate on buccal and lingual surfaces and microradiographed alongside an aluminium step-wedge for computerized quantitative microradiography. Mean mineralization values and mineralization frequency distribution curves were calculated. Gender had no effect on the mean mineralization values, but did show a significant difference in the mineralization frequency distribution. There was no difference in mean mineralization between lingual and buccal cortical plates, but the distribution curves differed, with the lingual cortex distributions being more uniform. Each sample site was significantly different from all others, with the mental foramen and body sites showing the greatest variation in distribution of mineralization level.

Mineralization differences between human deciduous and permanent enamel measured by quantitative microradiography.

The mineralization levels of erupted buccal enamel from 24 deciduous teeth were compared to those of 28 permanent teeth. Sections were prepared in a defined plane using a lapping machine which gave plano-parallel sections. Mineralization levels were recorded by quantitative microradiography at 25 equivalent anatomical sites in each section. Deciduous incisors and canines were compared with their homologous successors: overall mineralization levels were lower in the deciduous dentition, with no significant differences being found close to the amelo-dentinal junction, but highly significant differences being found in the outermost sites. Deciduous molars were compared with premolars, and were also relatively less mineralized. However, deciduous molars did not show the consistent diminishing occlusocervical gradient observed in all other tooth types tested; on the contrary, they showed a cervical reversal with higher values than permanent premolar enamel. These results confirm the generally lower mineral levels in deciduous enamel, and provide quantitative information on site-specific mineralization levels.

Crown-formation time of a fossil hominid premolar tooth.

Studies using surface or internal enamel growth indicators in hominids have suggested that crown-formation times were shorter than those in modern man. The crown-formation time in a robust australopithecine premolar tooth was calculated by counting enamel cross-striations, which correspond to daily increments of formation, on a replica of the fractured internal enamel surface of cuspal enamel using scanning electron microscopy. Cervical enamel completion time was estimated using other growth indicators including striae, and using measured and calculated cross-striation repeat intervals, giving a completion time of approx. 2.4 yr. This is much shorter than reported premolar crown formation times in modern man. These findings support the concept of an abbreviated period of dental development, with implications on the duration of the growth period in early hominids.

Percutaneous titanium implantation in the skull for the bone-anchored hearing aid.

In the 1980s, a new type of bone conduction hearing aid was developed in Göteborg, Sweden. With this new bone-anchored hearing aid (BAHA) system, sound waves are transmitted directly to the skull by means of a titanium screw implanted into the skull. The advantages and disadvantages of the conventional hearing aid and the BAHA are described here. In the 25 patients presented, all the percutaneous implants remained firmly anchored in the skull. One screw was lost through trauma. The scores on the speech recognition-in-noise and the speech recognition-in-quiet tests were significantly higher in 64% and 32% of the patients with a BAHA, respectively.

Binaural application of the bone-anchored hearing aid.

Most, but not all, hearing-impaired patients with air conduction hearing aids prefer binaural amplification instead of monaural amplification. The binaural application of the bone conduction hearing aid is more disputable, because the attenuation (in decibels) of sound waves across the skull is so small ( 10 dB) that even one bone conduction hearing aid will stimulate both cochleas approximately to the same extent. Binaural fitting of the bone-anchored hearing aid was studied in three experienced bone-anchored hearing aid users. The experiments showed that sound localization, and speech recognition in quiet and also under certain noisy conditions improved significantly with binaural listening compared to the monaural listening condition. On the average, the percentage of correct identifications (within 45 degrees ) in the sound localization experiment improved by 53% with binaural listening; the speech reception threshold in quiet improved by 4.4 dB. The binaural advantage in the speech-in-noise test was comparable to that of a control group of subjects with normal hearing listening monaurally versus binaurally. The improvements in the scores were ascribed to diotic summation (improved speech recognition in quiet) and the ability to separate sounds in the binaural listening condition (improved sound localization and improved speech recognition in noise whenever the speech and noise signals came from different directions). All three patients preferred the binaural bone-anchored hearing aids and used them all day.

Clinical considerations from axon-myelin relationship in human inferior alveolar nerve.

A histological study analysed the axon-myelin relationships in human inferior alveolar nerve fibres in both transverse and longitudinal sections. Observations on fibres cut in transverse section showed variation in myelin thickness upon axons having approximately the same diameter. Large diameter axons had relatively thinner myelin sheaths than small-diameter axons. A longitudinal reconstruction of a 470 micron length of fibre demonstrated the presence of 13 Schmidt-Lantermann clefts. The surgical and clinical implications of these finding are discussed.

Unmasking and abolition of Sudanophilia of the mineralizing front.

The effect of various treatments on the Sudanophilia of the mineralizing fronts of hard tissues has been examined. We have shown that a variety of organic solvents, but not all lipid unmasking protocols, expose Sudanophilic lipids at the mineralizing fronts of dentine, enamel matrix, bone and cartilage by the extraction of a substance which is not Sudanophilic. A variety of organic solvents, but not all extraction protocols, abolish Sudanophilia at the mineralizing fronts of bone and cartilage. The present study indicates that only solvent mixtures containing methanol abolished Sudanophilia at the mineralizing fronts of dentine and enamel matrix.

Adhesion of composite resin to bone--a pilot study.

This pilot study investigated the adhesion of composite resin to pig calvarium using All-bond 2 dentine bonding agent in an in vitro model. The bone was subjected to different methods of preparation. Acid-etching decreased the bond strength between bone and composite. Roughening the bone with a surgical bur prior to application of the adhesive produced bond strengths in the range 11.1-16.1 MPa.

[A hearing aid anchored in the cranial bone for amplification of bone conduction]. / Een in het schedelbeen verankerd hoortoestel voor versterking van de beengeleiding.

The purpose of this study was to compare hearing and understanding with a bone conduction hearing aid of a new type and with conventional models. The new instrument, BAHA (bone anchored hearing aid) is connected with the skull percutaneously rather than transcutaneously as with the conventional instruments. In the ENT department of Nijmegen University Hospital the understanding of speech with both types of hearing aid was evaluated thoroughly. The patients had a middle-ear loss with in addition an inner-ear loss of 60 dBHL at most. A conventional air conduction hearing aid (behind or inside the ear) was unsuitable for them because of, for instance, chronic runny ears or anomalies of the auditory meatus. A conventional bone conduction hearing aid containing a transducer pressing on the skin was rejected because of poor understanding or serious side effects such as headache and pressure pains. At the first session a titanium screw was implanted in the skull behind the ear. The percutaneous superstructure was put into place a few months later at a second session. In none of the patients were there peroperative problems or postoperative infections of any importance. Understanding of speech in silence and in noise was evaluated with the BAHA and with the conventional aid. Differences in understanding of speech were regarded as significant if they amounted to more than twice the known intra-individual standard deviation. As to understanding of speech in silence, 7 of the 15 patients were found to understand significantly better with the BAHA than with a conventional aid. In the other patients no difference was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Progressive hereditary hearing impairment caused by a MYO6 mutation resembles presbyacusis.

Since deafness is the most common sensorineural disorder in humans, better understanding of the underlying causes is necessary to improve counseling and rehabilitation. A Dutch family with autosomal dominantly inherited sensorineural hearing loss was clinically and genetically assessed. The MYO6 gene was selected to be sequenced because of similarities with other, previously described DFNA22 phenotypes and a pathogenic c.3610C > T (p.R1204W) mutation was found to co-segregate with the disease. This missense mutation results in a flat configured audiogram with a mild hearing loss, which becomes severe to profound and gently to steeply downsloping later in life. The age-related typical audiograms (ARTA) constructed for this family resemble presbyacusis. Speech audiometry and results of loudness scaling support the hypothesis that the phenotype of this specific MYO6 mutation mimics presbyacusis.