Electrically evoked auditory cortical responses elicited from individually fitted stimulation parameters in cochlear implant users.

OBJECTIVE: To investigate electrically evoked auditory cortical responses (eACR) elicited from the stimulation of intracochlear electrodes based on individually fitted stimulation parameters in cochlear implant (CI) users. DESIGN: An eACR setup based on individual fitting parameters is proposed. A 50-ms alternating biphasic pulse train was used to stimulate apical, medial, and basal electrodes and to evoke auditory cortical potentials (N1-P2 complex). STUDY SAMPLE: The eACR setup proposed was validated with 14 adult CI users. RESULTS: Individual and grand-average eACR waveforms were obtained. The eACR amplitudes were lower in the basal than in the apical and medial regions. Earlier N1 latencies were found in CI users with lower maximum comfortable loudness levels and shorter phase duration in response to apical stimulation, while medial and basal stimulation resulted in earlier N1 latencies and larger N1-P2 amplitudes in users with longer CI experience. CONCLUSIONS: eACR could be elicited by direct intracochlear stimulation using individual fitting parameters with a success rate of 71%. The highest cortical peak-to-peak amplitudes were obtained in response to apical stimulation. Unlike the P2, the N1 component appeared to be a consistent cortical potential to determine eACR and gain knowledge of the auditory processing beyond the cochlea in CI users. HighlightseACR can be elicited through direct stimulation of intracochlear electrodes.Stimulation of apical and medial regions yielded the highest N1-P2 amplitudes.CI users with lower maximum comfortable loudness levels had shorter N1 latencies during apical stimulation.The present dataset of mainly well-performing CI users suggests better cortical processing, that is, higher amplitudes and shorter latencies of N1.The N1 potential appears a more consistent and reliable potential than the P2 to determine eACR responses in CI users.

A retrospective cohort study exploring the association between different mitochondrial diseases and hearing loss.

Some pathogenic variants in mtDNA and nuclear DNA, affecting mitochondrial function, are associated with hearing loss. Behavioral and electrophysiological auditory performance are obtained from 62 patients, clinically diagnosed with different mitochondrial diseases (MD) using tone/speech audiometry and Auditory Brainstem Responses (ABR). Audiological variables (hearing loss type, pure tone average (PTA), interaural asymmetry, speech perception and brainstem neural conductivity) were analyzed and related to Newcastle Mitochondrial Disease Scale for Adults (NMDAS). In 35% of MDs, a mild to severe symmetrical sensorineural hearing loss (SNHL) was found. Patients with Maternally Inherited Diabetes and Deafness (MIDD) show significantly higher PTAs compared to other MDs. For all MDs, speech recognition scores were in accordance with their individual age- and gender-corrected tone audiometry, but ABR peak latencies were prolonged in patients with MIDD, Mitochondrial Encephalopathy Lactate acidosis and Stroke-like episodes (MELAS), Chronic Progressive External Ophthalmoplegia (CPEO) and Subacute necrotizing encephalopathy (Leigh). Correlations between NMDAS and audiological variables were low.

Auditory brainstem response prior to MRI compared to standalone MRI in the detection of vestibular schwannoma: A modelling study.

OBJECTIVES: To determine the cost-effectiveness of auditory brainstem response prior to MRI (ABR-MRI) compared to standalone MRI to diagnose vestibular schwannoma. DESIGN: A state transition model was developed to simulate costs and effects (quality-adjusted life years [QALY]) for both diagnostic strategies for patients suspected of a vestibular schwannoma. Model input was derived from literature, hospital databases and expert opinions. Scenario and sensitivity analyses addressed model uncertainty. RESULTS: Over a lifetime horizon, ABR-MRI resulted in a limited cost-saving of €68 or €98 per patient (dependent on MRI sequence) and a health loss of 0.005 QALYs over standalone MRI. ABR-MRI, however, did miss patients with other important pathology (2% of the population) that would have been detected when using standalone MRI. In total, €14 203 or €19 550 could be saved per lost QALY if ABR-MRI was used instead of standalone MRI. The results were sensitive to the detection rate of vestibular schwannoma and health-related quality of life of missed patients. CONCLUSION: The cost-saving with ABR-MRI does not seem to outweigh the number of missed patients with VS and other important pathologies that would have been detected when using standalone MRI.

MPZL2, Encoding the Epithelial Junctional Protein Myelin Protein Zero-like 2, Is Essential for Hearing in Man and Mouse.

In a Dutch consanguineous family with recessively inherited nonsyndromic hearing impairment (HI), homozygosity mapping combined with whole-exome sequencing revealed a MPZL2 homozygous truncating variant, c.72del (p.Ile24Metfs∗22). By screening a cohort of phenotype-matched subjects and a cohort of HI subjects in whom WES had been performed previously, we identified two additional families with biallelic truncating variants of MPZL2. Affected individuals demonstrated symmetric, progressive, mild to moderate sensorineural HI. Onset of HI was in the first decade, and high-frequency hearing was more severely affected. There was no vestibular involvement. MPZL2 encodes myelin protein zero-like 2, an adhesion molecule that mediates epithelial cell-cell interactions in several (developing) tissues. Involvement of MPZL2 in hearing was confirmed by audiometric evaluation of Mpzl2-mutant mice. These displayed early-onset progressive sensorineural HI that was more pronounced in the high frequencies. Histological analysis of adult mutant mice demonstrated an altered organization of outer hair cells and supporting cells and degeneration of the organ of Corti. In addition, we observed mild degeneration of spiral ganglion neurons, and this degeneration was most pronounced at the cochlear base. Although MPZL2 is known to function in cell adhesion in several tissues, no phenotypes other than HI were found to be associated with MPZL2 defects. This indicates that MPZL2 has a unique function in the inner ear. The present study suggests that deleterious variants of Mplz2/MPZL2 affect adhesion of the inner-ear epithelium and result in loss of structural integrity of the organ of Corti and progressive degeneration of hair cells, supporting cells, and spiral ganglion neurons.

A RIPOR2 in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss.

BACKGROUND: Hearing loss is one of the most prevalent disabilities worldwide, and has a significant impact on quality of life. The adult-onset type of the condition is highly heritable but the genetic causes are largely unknown, which is in contrast to childhood-onset hearing loss. METHODS: Family and cohort studies included exome sequencing and characterisation of the hearing phenotype. Ex vivo protein expression addressed the functional effect of a DNA variant. RESULTS: An in-frame deletion of 12 nucleotides in RIPOR2 was identified as a highly penetrant cause of adult-onset progressive hearing loss that segregated as an autosomal dominant trait in 12 families from the Netherlands. Hearing loss associated with the deletion in 63 subjects displayed variable audiometric characteristics and an average (SD) age of onset of 30.6 (14.9) years (range 0-70 years). A functional effect of the RIPOR2 variant was demonstrated by aberrant localisation of the mutant RIPOR2 in the stereocilia of cochlear hair cells and failure to rescue morphological defects in RIPOR2-deficient hair cells, in contrast to the wild-type protein. Strikingly, the RIPOR2 variant is present in 18 of 22 952 individuals not selected for hearing loss in the Southeast Netherlands. CONCLUSION: Collectively, the presented data demonstrate that an inherited form of adult-onset hearing loss is relatively common, with potentially thousands of individuals at risk in the Netherlands and beyond, which makes it an attractive target for developing a (genetic) therapy.

Impact of cochlear implantation on the function of the three semicircular canals.

OBJECTIVE: To assess the effect of cochlear implantation on the function of the semicircular canals (SCC) and on experienced vestibular symptoms. Second, to determine the relation between vestibular test results. DESIGN: Retrospective cohort study assessing absolute and categorised results of caloric irrigation test, video Head Impulse Test (vHIT) and Dizziness Handicap Inventory (DHI) before and after cochlear implantation.Study sample: 192 patients, aged ≥7 years old, without preoperative areflexia. RESULTS: Mean maximum slow phase velocity decreased with 3.1°/s and 4.7°/s for warm and cold caloric irrigation respectively. About 37.4% of the patients deteriorated one or more categories on caloric testing. Complete caloric postoperative areflexia was found in 6.2%. Mean vHIT gain decreased with 0.06, 0.04 and 0.05 for anterior, lateral and posterior SCC, respectively. Seven patients (7.7%) acquired an abnormal gain value for the anterior SCC. Only mean score on DHI's physical subdomain rose significantly (1.4 points). Overall, 9.0% of the patients deteriorated one or two categories on DHI. Only few weak correlations were found between caloric test, vHIT and DHI shifts. CONCLUSIONS: Although mean objective and subjective-physical vestibular deteriorations were significant, its clinical impact seems limited. However, 9% of patients experience vestibular deterioration, thus, advocate assessment. Vestibular test results show no or merely weak mutual correlations.

The P300 auditory event-related potential as a method to assess the benefit of contralateral hearing aid use in bimodal listeners: a proof-of-concept.

Objective: Bimodal listeners vary in the amount of benefit they receive from wearing the contralateral hearing aid. This may partially depend on the listener's auditory processing capacities. The current study explores whether the P300 event-related potential can provide insight into the mechanisms underlying the benefits of wearing a contralateral hearing aid.Design: P300s were recorded using an oddball paradigm with 500 and 250 Hz tone-bursts as standard and deviant stimuli, respectively. Subjects counted the number of deviants - a measure of performance. N2b latencies, P300 latencies, N2b-P300 amplitudes, and performance were assessed during CI-only and bimodal listening.Study sample: Five bimodal listeners.Results: P300s were present in four subjects. Amplitudes were larger during bimodal listening (bimodal: 22.3 ± 4.83 µV, CI-only: 13.1 ± 3.86 µV). Both N2b and P300 latencies were shorter during bimodal (N2b: 265 ± 20.0 ms, P300: 551 ± 129.4 ms) than CI-only listening (N2b: 326 ± 42.2 ms, P300: 402 ± 38.4 ms). While performance often reached ceiling level, the difference between the standard and deviant was generally more salient during bimodal listening.Conclusions: This study provides a proof-of-concept, suggesting that P300s may provide insight into benefits that are not always measurable with behavioural tasks.

De novo and inherited loss-of-function variants of ATP2B2 are associated with rapidly progressive hearing impairment.

ATP2B2 encodes the PMCA2 Ca2+ pump that plays an important role in maintaining ion homeostasis in hair cells among others by extrusion of Ca2+ from the stereocilia to the endolymph. Several mouse models have been described for this gene; mice heterozygous for loss-of-function defects display a rapidly progressive high-frequency hearing impairment. Up to now ATP2B2 has only been reported as a modifier, or in a digenic mechanism with CDH23 for hearing impairment in humans. Whole exome sequencing in hearing impaired index cases of Dutch and Polish origins revealed five novel heterozygous (predicted to be) loss-of-function variants of ATP2B2. Two variants, c.1963G>T (p.Glu655*) and c.955delG (p.Ala319fs), occurred de novo. Three variants c.397+1G>A (p.?), c.1998C>A (p.Cys666*), and c.2329C>T (p.Arg777*), were identified in families with an autosomal dominant inheritance pattern of hearing impairment. After normal newborn hearing screening, a rapidly progressive high-frequency hearing impairment was diagnosed at the age of about 3-6 years. Subjects had no balance complaints and vestibular testing did not yield abnormalities. There was no evidence for retrocochlear pathology or structural inner ear abnormalities. Although a digenic inheritance pattern of hearing impairment has been reported for heterozygous missense variants of ATP2B2 and CDH23, our findings indicate a monogenic cause of hearing impairment in cases with loss-of-function variants of ATP2B2.

Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction.

Unraveling the causes and pathomechanisms of progressive disorders is essential for the development of therapeutic strategies. Here, we identified heterozygous pathogenic missense variants of LMX1A in two families of Dutch origin with progressive nonsyndromic hearing impairment (HI), using whole exome sequencing. One variant, c.721G > C (p.Val241Leu), occurred de novo and is predicted to affect the homeodomain of LMX1A, which is essential for DNA binding. The second variant, c.290G > C (p.Cys97Ser), predicted to affect a zinc-binding residue of the second LIM domain that is involved in protein-protein interactions. Bi-allelic deleterious variants of Lmx1a are associated with a complex phenotype in mice, including deafness and vestibular defects, due to arrest of inner ear development. Although Lmx1a mouse mutants demonstrate neurological, skeletal, pigmentation and reproductive system abnormalities, no syndromic features were present in the participating subjects of either family. LMX1A has previously been suggested as a candidate gene for intellectual disability, but our data do not support this, as affected subjects displayed normal cognition. Large variability was observed in the age of onset (a)symmetry, severity and progression rate of HI. About half of the affected individuals displayed vestibular dysfunction and experienced symptoms thereof. The late-onset progressive phenotype and the absence of cochleovestibular malformations on computed tomography scans indicate that heterozygous defects of LMX1A do not result in severe developmental abnormalities in humans. We propose that a single LMX1A wild-type copy is sufficient for normal development but insufficient for maintenance of cochleovestibular function. Alternatively, minor cochleovestibular developmental abnormalities could eventually lead to the progressive phenotype seen in the families.

Age-Related Changes in Binaural Interaction at Brainstem Level.

OBJECTIVES: Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The present study investigates binaural interaction at the level of the auditory brainstem. It is hypothesized that brainstem binaural interaction deteriorates with advancing age. DESIGN: Forty-two subjects of various age participated in the study. Auditory brainstem responses (ABRs) were recorded using clicks and 500 Hz tone-bursts. ABRs were elicited by monaural right, monaural left, and binaural stimulation. Binaural interaction was investigated in two ways. First, grand averages of the binaural interaction component were computed for each age group. Second, wave V characteristics of the binaural ABR were compared with those of the summed left and right ABRs. RESULTS: Binaural interaction in the click ABR was demonstrated by shorter latencies and smaller amplitudes in the binaural compared with the summed monaural responses. For 500 Hz tone-burst ABR, no latency differences were found. However, amplitudes were significantly smaller in the binaural than summed monaural condition. An age-effect was found for 500 Hz tone-burst, but not for click ABR. CONCLUSIONS: Brainstem binaural interaction seems to decline with age. Interestingly, these changes seem to be stimulus-dependent.

Hippocampal dysfunction in the Euchromatin histone methyltransferase 1 heterozygous knockout mouse model for Kleefstra syndrome.

Euchromatin histone methyltransferase 1 (EHMT1) is a highly conserved protein that catalyzes mono- and dimethylation of histone H3 lysine 9, thereby epigenetically regulating transcription. Kleefstra syndrome (KS), is caused by haploinsufficiency of the EHMT1 gene, and is an example of an emerging group of intellectual disability (ID) disorders caused by genes encoding epigenetic regulators of neuronal gene activity. Little is known about the mechanisms underlying this disorder, prompting us to study the Euchromatin histone methyltransferase 1 heterozygous knockout (Ehmt1(+/-)) mice as a model for KS. In agreement with the cognitive disturbances observed in patients with KS, we detected deficits in fear extinction learning and both novel and spatial object recognition in Ehmt1(+/-) mice. These learning and memory deficits were associated with a significant reduction in dendritic arborization and the number of mature spines in hippocampal CA1 pyramidal neurons of Ehmt1(+/-) mice. In-depth analysis of the electrophysiological properties of CA3-CA1 synapses revealed no differences in basal synaptic transmission or theta-burst induced long-term potentiation (LTP). However, paired-pulse facilitation (PPF) was significantly increased in Ehmt1(+/-) neurons, pointing to a potential deficiency in presynaptic neurotransmitter release. Accordingly, a reduction in the frequency of miniature excitatory post-synaptic currents (mEPSCs) was observed in Ehmt1(+/-) neurons. These data demonstrate that Ehmt1 haploinsufficiency in mice leads to learning deficits and synaptic dysfunction, providing a possible mechanism for the ID phenotype in patients with KS.

Mutations of the gene encoding otogelin are a cause of autosomal-recessive nonsyndromic moderate hearing impairment.

Already 40 genes have been identified for autosomal-recessive nonsyndromic hearing impairment (arNSHI); however, many more genes are still to be identified. In a Dutch family segregating arNSHI, homozygosity mapping revealed a 2.4 Mb homozygous region on chromosome 11 in p15.1-15.2, which partially overlapped with the previously described DFNB18 locus. However, no putative pathogenic variants were found in USH1C, the gene mutated in DFNB18 hearing impairment. The homozygous region contained 12 additional annotated genes including OTOG, the gene encoding otogelin, a component of the tectorial membrane. It is thought that otogelin contributes to the stability and strength of this membrane through interaction or stabilization of its constituent fibers. The murine orthologous gene was already known to cause hearing loss when defective. Analysis of OTOG in the Dutch family revealed a homozygous 1 bp deletion, c.5508delC, which leads to a shift in the reading frame and a premature stop codon, p.Ala1838ProfsX31. Further screening of 60 unrelated probands from Spanish arNSHI families detected compound heterozygous OTOG mutations in one family, c.6347C>T (p.Pro2116Leu) and c. 6559C>T (p.Arg2187X). The missense mutation p.Pro2116Leu affects a highly conserved residue in the fourth von Willebrand factor type D domain of otogelin. The subjects with OTOG mutations have a moderate hearing impairment, which can be associated with vestibular dysfunction. The flat to shallow "U" or slightly downsloping shaped audiograms closely resembled audiograms of individuals with recessive mutations in the gene encoding α-tectorin, another component of the tectorial membrane. This distinctive phenotype may represent a clue to orientate the molecular diagnosis.

Similar phenotypes caused by mutations in OTOG and OTOGL.

OBJECTIVES: Recently, OTOG and OTOGL were identified as human deafness genes. Currently, only four families are known to have autosomal recessive hearing loss based on mutations in these genes. Because the two genes code for proteins (otogelin and otogelin-like) that are strikingly similar in structure and localization in the inner ear, this study is focused on characterizing and comparing the hearing loss caused by mutations in these genes. DESIGN: To evaluate this type of hearing, an extensive set of audiometric and vestibular examinations was performed in the 13 patients from four families. RESULTS: All families show a flat to downsloping configuration of the audiogram with mild to moderate sensorineural hearing loss. Speech recognition scores remain good (>90%). Hearing loss is not significantly different in the four families and the psychophysical test results also do not differ among the families. Vestibular examinations show evidence for vestibular hyporeflexia. CONCLUSION: Because otogelin and otogelin-like are localized in the tectorial membrane, one could expect a cochlear conductive hearing loss, as was previously shown in DFNA13 (COL11A2) and DFNA8/12 (TECTA) patients. Results of psychophysical examinations, however, do not support this. Furthermore, the authors conclude that there are no phenotypic differences between hearing loss based on mutations in OTOG or OTOGL. This phenotype description will facilitate counseling of hearing loss caused by defects in either of these two genes.

Genotype and Phenotype Analyses of a Novel WFS1 Variant (c.2512C>T p.(Pro838Ser)) Associated with DFNA6/14/38.

The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch-German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband. Co-segregation of the identified variant with hearing loss was assessed by Sanger sequencing. The phenotypic evaluation consisted of anamnesis, clinical questionnaires, physical examination and examination of audiovestibular function. A novel likely pathogenic WFS1 variant (NM_006005.3:c.2512C>T p.(Pro838Ser)) was identified in the proband and found to co-segregate with LFSNHL, characteristic of DFNA6/14/38, in this family. The self-reported age of onset of hearing loss (HL) ranged from congenital to 50 years of age. In the young subjects, HL was demonstrated in early childhood. At all ages, an LFSNHL (0.25-2 kHz) of about 50-60 decibel hearing level (dB HL) was observed. HL in the higher frequencies showed inter-individual variability. The dizziness handicap inventory (DHI) was completed by eight affected subjects and indicated a moderate handicap in two of them (aged 77 and 70). Vestibular examinations (n = 4) showed abnormalities, particularly in otolith function. In conclusion, we identified a novel WFS1 variant that co-segregates with DFNA6/14/38 in this family. We found indications of mild vestibular dysfunction, although it is uncertain whether this is related to the identified WFS1 variant or is an incidental finding. We would like to emphasize that conventional neonatal hearing screening programs are not sensitive to HL in DFNA6/14/38 patients, because high-frequency hearing thresholds are initially preserved. Therefore, we suggest screening newborns in DFNA6/14/38 families with more frequency-specific methods.

ATP8B1 is essential for maintaining normal hearing.

ATP8B1 deficiency is caused by autosomal recessive mutations in ATP8B1, which encodes the putative phospatidylserine flippase ATP8B1 (formerly called FIC1). ATP8B1 deficiency is primarily characterized by cholestasis, but extrahepatic symptoms are also found. Because patients sometimes report reduced hearing capability, we investigated the role of ATP8B1 in auditory function. Here we show that ATP8B1/Atp8b1 deficiency, both in patients and in Atp8b1(G308V/G308V) mutant mice, causes hearing loss, associated with progressive degeneration of cochlear hair cells. Atp8b1 is specifically localized in the stereocilia of these hair cells. This indicates that the mechanosensory function and integrity of the cochlear hair cells is critically dependent on ATP8B1 activity, possibly through maintaining lipid asymmetry in the cellular membranes of stereocilia.

Genotype-Phenotype Correlations of Pathogenic COCH Variants in DFNA9: A HuGE Systematic Review and Audiometric Meta-Analysis.

Pathogenic missense variants in COCH are associated with DFNA9, an autosomal dominantly inherited type of progressive sensorineural hearing loss with or without vestibular dysfunction. This study is a comprehensive overview of genotype-phenotype correlations using the PRISMA and HuGENet guidelines. Study characteristics, risk of bias, genotyping and data on the self-reported age of onset, symptoms of vestibular dysfunction, normative test results for vestibular function, and results of audiovestibular examinations were extracted for each underlying pathogenic COCH variant. The literature search yielded 48 studies describing the audiovestibular phenotypes of 27 DFNA9-associated variants in COCH. Subsequently, meta-analysis of audiometric data was performed by constructing age-related typical audiograms and by performing non-linear regression analyses on the age of onset and progression of hearing loss. Significant differences were found between the calculated ages of onset and progression of the audiovestibular phenotypes of subjects with pathogenic variants affecting either the LCCL domain of cochlin or the vWFA2 and Ivd1 domains. We conclude that the audiovestibular phenotypes associated with DFNA9 are highly variable. Variants affecting the LCCL domain of cochlin generally lead to more progression of hearing loss when compared to variants affecting the other domains. This review serves as a reference for prospective natural history studies in anticipation of mutation-specific therapeutic interventions.

Kidney failure in mice lacking the tetraspanin CD151.

The tetraspanin CD151 is a cell-surface molecule known for its strong lateral interaction with the laminin-binding integrin alpha3beta1. Patients with a nonsense mutation in CD151 display end-stage kidney failure associated with regional skin blistering and sensorineural deafness, and mice lacking the integrin alpha3 subunit die neonatally because of severe abnormalities in the lung and kidney epithelia. We report the generation of Cd151-null mice that recapitulate the renal pathology of human patients, i.e., with age they develop massive proteinuria caused by focal glomerulosclerosis, disorganization of the glomerular basement membrane, and tubular cystic dilation. However, neither skin integrity nor hearing ability are impaired in the Cd151-null mice. Furthermore, we generated podocyte-specific conditional knockout mice for the integrin alpha3 subunit that show renal defects similar to those in the Cd151 knockout mice. Our results support the hypothesis that CD151 plays a key role in strengthening alpha3beta1-mediated adhesion in podocytes.

Prediction of vestibular schwannoma growth: a novel rule based on clinical symptomatology.

OBJECTIVES: The aim of this study was to formulate a predictive rule for vestibular schwannoma growth during the initial observation period after diagnosis. METHODS: Logistic regression models were fitted, with tumor growth in the first year as the dependent variable and patient characteristics as the independent variables. Backward selection was used to eliminate superfluous predictors. The area under the receiver operating characteristic curve was taken as a measure of the model's discriminative power. RESULTS: Eventually, the model or rule consisted of 4 significant growth predictors: localization (if extrameatal, +1; if intrameatal, 0), sudden sensorineural hearing loss (if present, -1; if absent, 0), balance symptoms (if present, +1; if absent, 0), and complaints of hearing loss for less than 2 years (if present, +1; if absent, or present for more than 2 years, 0). A higher score indicates a higher likelihood of tumor growth during the period of observation after diagnosis. If the total score is 0 or less, the likelihood of tumor growth during the first year after diagnosis is less than 10%. If the score is 3, the likelihood of growth during the first year after diagnosis is more than 70%. CONCLUSIONS: We were able to create a useful rule to predict vestibular schwannoma growth during the first year after diagnosis.

Use of an Extra-Tympanic Membrane Electrode to Record Cochlear Microphonics with Click, Tone Burst and Chirp Stimuli.

This study determined electrocochleography (ECochG) parameter settings to obtain cochlear microphonics (CM) with less invasive flexible extra-tympanic membrane electrodes. In 24 adult normal-hearing subjects, CMs were elicited by presenting click stimuli at 100 dBnHL, tone bursts (2 kHz) and broadband (BB) CE-chirps® LS (Interacoustics, Middelfart, Denmark), both at 80 dBnHL. Different high-pass filters (HPFs) (3.3 Hz and 100 Hz, respectively) were used to investigate response quality of the CM. CMs were successfully obtained in 92-100% with click-, 75-83% with 2 kHz tone burst- and 58-63% with CE-chirp®-LS stimuli. Click stimuli elicited significantly larger CM amplitudes compared to 2 kHz tone bursts and BB CE-chirp® LS (Interacoustics, Middelfart, Denmark). No significant differences were found between the two different high-pass filter (HPF) settings. The present study shows that it is possible to obtain clear CMs with the flexible extra-tympanic membrane electrodes using click stimuli. In contrast to 2 kHz tone bursts and CE-chirp® (Interacoustics, Middelfart, Denmark) LS, clicks show a significantly higher success rate and are the preferred stimuli to confirm the presence or absence of CMs.

Intracorporeal Cortical Telemetry as a Step to Automatic Closed-Loop EEG-Based CI Fitting: A Proof of Concept.

Electrically evoked auditory potentials have been used to predict auditory thresholds in patients with a cochlear implant (CI). However, with exception of electrically evoked compound action potentials (eCAP), conventional extracorporeal EEG recording devices are still needed. Until now, built-in (intracorporeal) back-telemetry options are limited to eCAPs. Intracorporeal recording of auditory responses beyond the cochlea is still lacking. This study describes the feasibility of obtaining longer latency cortical responses by concatenating interleaved short recording time windows used for eCAP recordings. Extracochlear reference electrodes were dedicated to record cortical responses, while intracochlear electrodes were used for stimulation, enabling intracorporeal telemetry (i.e., without an EEG device) to assess higher cortical processing in CI recipients. Simultaneous extra- and intra-corporeal recordings showed that it is feasible to obtain intracorporeal slow vertex potentials with a CI similar to those obtained by conventional extracorporeal EEG recordings. Our data demonstrate a proof of concept of closed-loop intracorporeal auditory cortical response telemetry (ICT) with a cochlear implant device. This research breaks new ground for next generation CI devices to assess higher cortical neural processing based on acute or continuous EEG telemetry to enable individualized automatic and/or adaptive CI fitting with only a CI.