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.

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.

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.

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.

Normative findings of electrically evoked compound action potential measurements using the neural response telemetry of the Nucleus CI24M cochlear implant system.

One hundred and forty-seven adult recipients of the Nucleus 24 cochlear implant system, from 13 different European countries, were tested using neural response telemetry to measure the electrically evoked compound action potential (ECAP), according to a standardised postoperative measurement procedure. Recordings were obtained in 96% of these subjects with this standardised procedure. The group results are presented in terms of peak amplitude and latency, slope of the amplitude growth function and ECAP threshold. The effects of aetiological factors and the duration of deafness on the ECAP were also studied. While large intersubject variability and intrasubject variability (across electrodes) were found, results fell within a consistent pattern and a normative range of peak amplitudes and latencies was established. The aetiological factors had little effect on the ECAP characteristics. However, age affected ECAP amplitude and slope of the amplitude growth function significantly; i.e., the amplitude is higher in the lowest age category (15-30 years). Principal component analysis of the ECAP thresholds shows that the thresholds across 5 electrodes can be described by two factors accounting for 92% of the total variance. The two factors represent the overall level of the threshold profiles ('shift') and their slopes across the electrode array ('tilt'). Correlation between these two factors and the same factors describing the T- and C-levels appeared to be moderate, in the range of 0.5-0.6.

Use of the event-related P300 potential in cochlear implant subjects for the study of strategy-dependent speech processing.

The present overview is a compilation of the results of several event-related potential (ERP) studies on auditory cortical processing, performed in the Evoked Potential Laboratory of the University Medical Centre of Nijmegen. To study speech perception performance in cochlear implant (CI) subjects, ERPs were obtained from subjects with poor and moderate performance. The present report describes the relationships between speech-coding strategies, the presentation of speech by the CI processor, the P300 potential as a measure of speech discrimination, time effects in the long term and speech recognition in relation to ERPs.

Speech-evoked cortical potentials and speech recognition in cochlear implant users.

Processing in the auditory cortex may play a role in the unexplained variability in cochlear implant benefit. P300 and N1/P2 were elicited in post-lingually deaf cochlear implant users wearing a Nucleus multichannel cochlear implant. Four sound contrasts were presented (500-1,000 Hz, /ba/-/da/, /ba/-/pa/ and /i/-/a/). N1 and P2 were present in all subjects for all conditions. Prolonged N1, P2 and P300 latencies were found in the cochlear implant group compared to a control group of subjects with normal hearing. Cochlear implant users show smaller amplitudes of N1 for all the speech signals as well as smaller amplitudes of P2 for the consonants compared to the controls. P300 results of the cochlear implant users were compared to behavioural results of speech recognition testing. A relation was found between P300 amplitude and magnitude for the 500-1,000 Hz and /i/-/a/ contrasts and behavioural speech recognition in cochlear implant users. The results suggest that P300 measurements are useful and have additional value to speech recognition evaluations in cochlear implant users.

Radiographic and histological methodologies in estimating the chronology of crown development in modern humans and great apes: a review, with some applications for studies on juvenile hominids.

There has been a burgeoning of interest in the last decade on growth studies in hominids. These studies have relied heavily on dental development, and have compared juvenile hominids to modern human and ape standards, which are usually established using radiographic data. There has been considerable discussion on the most appropriate methods of deriving population standards from radiographs, but very little on the accuracy of the radiographic image itself. Previous histological and dissection studies have shown that age at onset of mineralization is overestimated, and age at crown completion is underestimated using radiographs. This study considers the process of X-ray absorbence by mineralized tissues and the formation of radiographic images of developing teeth. Following tooth initiation a critical mass of mineral is required for the tooth to register superimposed on the absorbence of alveolar crypt bone, which accounts for the late identification of tooth initiation. Determination of completion of crown growth depends upon the identification of the last formed enamel at the cervix. Recognition of this key stage is difficult as crown growth slows towards the cervix, and the last secreted enamel may take months to attain full mineralization levels due to the prolonged maturation process. Morphological and geometric factors have a significant influence on the imaging of the completed crown. The last formed enamel is located on the buccal face, where enamel thins progressively to nothing. X-ray absorption by enamel at the cervix becomes insignificant, and may be counterbalanced by increased dentine absorption. Approximal enamel in contrast is clearly visualized once maturation is complete. However, developmentally this enamel face initiates later, and is completed much earlier than buccal enamel. All of the radiographic estimates of crown completion times are based upon interpretations of approximal enamel completion. These considerations suggest that the human population standards in current usage may not represent true anatomical and chronological stages of crown development, and care should be taken in referring juvenile hominids to these radiological standards.

Histological reconstruction of dental development in four individuals from a medieval site in Picardie, France.

The majority of dental development studies in modern humans are based on radiographic analysis. In comparison, very few full histological studies have been carried out. In the present study, the onset of enamel formation and crown formation time have been established by histological analysis of the complete dentition in a medieval French individual. Crown formation times were established for the dentition of three further individuals. The number of cross-striations between adjacent striae of Retzius was measured and accentuated striae were used to construct a chart of the chronology of tooth development. Results on crown formation times in individual teeth when compared with previous histologic studies are slightly greater than values in a modern African male and near to or less than values in (M1) and (I) respectively in a modern population from Spitalfields, London. Histologically derived crown initiation times are earlier than those reported for radiographic studies. Values for crown formation times derived in general from radiographic studies are less than those of our study. Attention has recently been focused on the overlap of molar development as a key character for distinguishing between humans and great apes. In this study, there is an overlap in crown formation between M1 and M2 of 0.27 years and a temporal delay of 1.7 years between M2 crown completion and the initiation of the M3.

Variations in molar enamel thickness among primates.

Because of its hardness, resistance to abrasion and its influence on crown morphology, molar enamel thickness is an important factor in adaptation of the dentition to the diet. Enamel thickness has also been discussed extensively in relation to the phylogenetic relationships among the hominoids. The aims of this study were: (1) to analyse enamel thickness/tooth size relationships among primates as a whole, and (2) to evaluate variations in enamel thickness among hominoids against the background of the other primates. We employed measures of tooth size, and of enamel thickness and quantity based on measurements of areas in longitudinal sections of 125 molars of 39 species. Among primates, there were two grades of enamel thickness, prosimians having thinner enamel for a given tooth size or body weight than anthropoids. The scaling of enamel thickness with tooth size and body weight tended to show positive allometry among anthropoids. Comparison of hominoid enamel thicknesses with that in anthropoids led to the conclusion that Hylobates has enamel of average thickness, Homo has thick enamel and Gorilla has thin enamel, while Pan and Pongo had average or thin enamel, depending on tooth type. These results may be relevant to considerations of hominoid evolution.

Comparative dental development and microstructure of Proconsul teeth from Rusinga Island, Kenya.

Eighteen histological sections were prepared from eleven teeth attributed to Proconsul heseloni and two molar teeth attributed to Proconsul nyanzae. Measurements of spacings and counts of daily incremental markings in both enamel and dentine were possible in the majority of these tooth sections. Measurements of the spacings and angles to the enamel dentine junction (EDJ) of regular striae of Retzius and of equivalent markings in dentine were also made. In addition to these measurements, counts of perikymata were made on replicas of all other Proconsul teeth housed in the National Museum of Kenya, Nairobi, that preserved good perikymata on any aspect of their tooth surface. The sequence of crown formation in Proconsul and the crown formation times of the enamel and dentine were estimated from these data. In addition, the rates of root extension were estimated using the formula derived for this purpose by Shellis (Archs. oral Biol. 29, 697-705, 1984) and estimates of the total period of root formation subsequently made for premolar and molar teeth based on measurements of root length. A composite chart of dental development for P. heseloni is presented which suggests M3 root completion was between six and seven years of age. In general Proconsul molar teeth have high stria angles to the EDJ, a high ratio of enamel formed with respect of dentine formed at the same time, median values of rates of enamel formation close to the EDJ in excess of 4 microns per day and the occasional presence of "S-shaped" striae in the lateral enamel. There is no evidence to suggest that Proconsul from Rusinga Island, Kenya, had relatively thin enamel on molar or premolar teeth. When all of these data are considered in a comparative context, Proconsul emerges overall as hominoid-like in its enamel and dentine microstructure and as most similar to Pongo but with some features shared with Pan and Homo. Similar data for other Miocene primates will have considerable bearing on how these data are interpreted. These new data on dental microanatomy and on dental development in Proconsul make a further contribution to our understanding of the total morphological picture of this early Miocene primate.

The mixed dentition and associated skull fragments of a juvenile fossil hominid from Sterkfontein, South Africa.

In April-May 1983, the late A.R. Hughes and his field team recovered more than 40 bone fragments and teeth from a single solution pocket of the Sterkfontein Formation. After preparation and reconstruction by JMC, it was recognised that these fragments represent a single juvenile individual (Stw 151), consisting of more than 40 cranial and dental parts, with mixed dentition. It constitutes the most complete set of jaws and teeth of an early hominid child since the Taung child was recovered in 1924. In this paper, the morphological and metrical features of the individual teeth are described. The other associated skull fragments (right ramus of the mandible, left petrous bone, right glenoid region) are also described. Comparisons are made with other South (and East) African fossil hominids. The beautiful preservation simultaneously of most of the deciduous teeth and of the permanent teeth exposed in their crypts allows an accurate analysis of the developmental sequence. A report on the dental developmental status of this juvenile is presented. On the basis of the microanatomical study of the developing permanent teeth, the estimated age at death is 5.2-5.3 years. Reconstructions of the maxillary and mandibular arcades are also offered. The morphological and metrical features of Stw 151 raise the possibility that it may represent a hominid more derived towards an early Homo condition than the rest of the A. africanus sample from Member 4.

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.

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.

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.

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.