Aetiology of Ludwig van Beethoven's hearing impairment: hypotheses over the past 100 years - A systematic review.

OBJECTIVES: Even 250 years after Beethoven's birth, the irrevocable cause of his hearing impairment remains unclear despite multiple publications by different professional groups. This study aimed to analyse the development of the most likely aetiologies during the last 100 years by a systematic review of the relevant medical literature. METHODS: A systematic review of medical literature in PubMed®, PubMed Central®, and Web of Science® for the period 1920-2020 was conducted. Medical publications between 1920 and 1935 were additionally searched manually by review of reference lists. Studies were eligible when a statement regarding the most likely aetiology of the hearing loss of Beethoven was the aimed objective of the publication. RESULTS: 48 publications were included. The following aetiologies were supposed: otosclerosis (n = 10), syphilis (n = 9), Paget's disease (n = 6), neural deafness (n = 5), immunopathy with inflammatory bowel disease, neural deafness with otosclerosis, sarcoidosis or lead intoxication (n = 2), and systemic lupus erythematosus, trauma, labyrinthitis or inner ear disease (n = 1). There is an ongoing effort with a mean publication frequency in this topic of 0.48/year. From 1920 to 1970, otolaryngologists were the group with the highest interest in this field (67%), whereas since 1971 most authors have belonged to non-otolaryngologic subspecialities (81%). CONCLUSION: Over the past 100 years, otosclerosis and syphilis were predominantly supposed to be the underlying causes. The hypothesis of syphilis-although rejected for a long time-has had a remarkable revival during the past 20 years. Regarding the outcome following therapeutic intervention by cochlear implantation, the differential diagnosis of neural deafness would be relevant today.

Spatial Hearing by Bilateral Cochlear Implant Users With Temporal Fine-Structure Processing.

Several studies have demonstrated the advantages of the bilateral vs. unilateral cochlear implantation in listeners with bilateral severe to profound hearing loss. However, it remains unclear to what extent bilaterally implanted listeners have access to binaural cues, e.g., accurate processing of interaural timing differences (ITDs) for low-frequency sounds (<1.5 kHz) and interaural level differences (ILDs) for high frequencies (>3 kHz). We tested 25 adult listeners, bilaterally implanted with MED-EL cochlear implant (CI) devices, with and without fine-structure (FS) temporal processing as encoding strategy in the low-frequency channels. In order to assess whether the ability to process binaural cues was affected by fine-structure processing, we performed psychophysical ILD and ITD sensitivity measurements and free-field sound localization experiments. We compared the results of the bilaterally implanted listeners with different numbers of FS channels. All CI listeners demonstrated good sensitivity to ILDs, but relatively poor to ITD cues. Although there was a large variability in performance, some bilateral CI users showed remarkably good localization skills. The FS coding strategy for bilateral CI hearing did not improve fine-structure ITD processing for spatial hearing on a group level. However, some CI listeners were able to exploit weakly informative temporal cues to improve their low-frequency spatial perception.

A new adhesive bone conduction hearing system effectively treats conductive hearing loss in children.

OBJECTIVES: Bone conduction hearing devices integrated in softbands (BCDSs) are frequently not well accepted by children with conductive hearing loss due to pressure on the head, sweating, or cosmetic stigma. A non-surgical hearing system (ADHEAR) uses a new bone conduction concept consisting of an audio processor connected to an adhesive adapter fixed behind the ear. This study is the first to evaluate the audiological and clinical outcome of this novel system, comparing it with conventional BCDSs in a short- and mid-term follow-up in children under 10 years of age. METHODS: The ADHEAR was compared to a BCDS in 10 children with conductive hearing loss (age: 0.7-9.7 years). Aided and unaided pure tone/behavioral observational audiometry and, if applicable, speech audiometry in quiet and noise were performed initially with both devices and after 8 weeks with the ADHEAR alone. The subjective hearing gain and usage of the new hearing system, as well as patients' and parents' satisfaction were assessed using questionnaires. RESULTS: The functional gain with the ADHEAR averaged over 0.5, 1, 2, and 4 kHz exceeded that of the conventional BCDS (35.6 dB ±â€¯15.1 vs. 29.9 dB ±â€¯14.6, p = .001, n = 9 ears). Speech perception in quiet and noise (n = 8) improved in the aided situation similarly for both hearing devices. The parents of 8 of 10 children evaluated the ADHEAR system as being useful. Minor wearing problems occurred occasionally. Eight children continued using the ADHEAR after the study, one received an active middle ear implant and one continued to use a BCDS. CONCLUSION: The ADHEAR system is a promising solution for children with conductive hearing loss or chronically draining ears.

Prognostic factors regarding the hearing outcome in severe to profound sudden sensorineural hearing loss treated by tympanotomy and sealing of labyrinthine windows after ineffective systemic corticosteroid application.

PURPOSE: Tympanotomy and sealing of labyrinthine membranes has become in some centers used to treat severe to profound sudden sensorineural hearing loss refractory to conservative treatment. The aim of this retrospective study was to determine which preoperative factors influence the likelihood of postoperative recovery according to different audiological assessment criteria. METHODS: The mean final hearing threshold, the hearing improvement, the probability of a complete recovery according to two different classifications, and probability of a significant recovery of 136 adult subjects were studied by univariate and multivariate analyses. RESULTS: The subject's mean postoperative 4-pure-tone-average was 63.9 ± 35.9 dB, the mean improvement was 42.8 ± 32.6 dB. Depending on the classification system used, 18.4-28.0% of subjects experienced a complete recovery. 77.2% of subjects had a significant hearing improvement. History of a pressure change (odds ratio (OR):4.6) was the only positive prognostic factor for hearing improvement. It also enhanced probability of experiencing a complete hearing recovery (OR: 2.8-6.3). Preoperative total deafness (OR: 1.5-1.9) and vertigo (OR: 3.3-4.6) were negative prognostic factors for the mean final hearing threshold and the probability of a complete hearing recovery. Patients with a preceding pressure change event achieved a complete recovery in 45.5-50.0%, those without such an event recovered completely only in 13.2-23.7%. CONCLUSION: Evaluating prognostic factors and the rate of complete hearing recovery are influenced by the underlying assessment parameters. In addition to the mean postoperative hearing threshold and hearing gain, the probability of regaining a serviceable hearing is clinically important for the individual and should be added to the assessment criteria in future studies.

Transmastoid implantability of an active transcutaneous bone conduction implant in adults with regard to the underlying pathology: a radiological simulation study.

OBJECTIVES: To compare the feasibility of transmastoid implantation of an active transcutaneous bone conduction device (BCD) in the most important pathologies of the temporal bone and the impact of implant lifts in adulthood. METHODS: First, clinical predominant pathologies for implantation of this BCD were evaluated by a literature review. Then, high-resolution CT of 240 temporal bones with neuro-otologic diseases (NOD), chronic otitis media (COM), or cholesteatoma, respectively, were investigated regarding their implantability, using a radiological simulation program. RESULTS: Chronic inflammatory diseases (CID) of the temporal bone with or without cholesteatoma account for most adults scheduled for an active BCD. Complete implantation was possible in almost all cases with NOD as well as COM, requiring an implant lift in 50% of COM and 20% of NOD (p = .025) cases. In contrast, in subjects with cholesteatoma, implantation required an additional tool in 92% of cases, leading to 59% implantability rate in these temporal bones. CONCLUSION: Adult subjects with CID of the temporal bone show more limiting anatomical conditions for transmastoid placement of an active transcutaneous BCD than those with single-sided deafness. Implant lifts increase the implantability significantly in subjects with COM and particularly in those with cholesteatoma.

Vibroplasty in Severe Congenital or Acquired Meatal Stenosis by Coupling an Active Middle Ear Implant to the Short Process of the Incus.

OBJECTIVE: To evaluate the safety and effectiveness of coupling an active middle ear implant to the short process of the incus in subjects with meatal pathologies. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: Twelve patients suffering from either congenital aural atresia or acquired meatal fibrosis. INTERVENTION: Implantation of an active middle ear implant with coupling of the actuator to the short process of the incus. MAIN OUTCOME MEASURES: Evaluation of the air conduction and bone conduction hearing thresholds pre- and postoperatively, aided warble-tone hearing thresholds, unaided and aided speech recognition in quiet and noise. Questionnaires on subjective benefit and quality of life. RESULTS: Mean unaided postoperative air conduction and bone conduction thresholds did not vary significantly from preoperative values (p = 0.55 and 0.082, respectively). The mean functional gain amounted to 42.1 ±â€Š8.8 dB, the mean aided sound field threshold of the implanted ear was 28.6 ±â€Š8.6 dB. No significant difference in functional gain but a close to significant difference in postoperative aided thresholds (p = 0.053) were found between subjects with congenital atresia and acquired fibrosis. Subjective benefit assessed by the global score of the Abbreviated Profile of Hearing Aid Benefit questionnaire revealed an improvement of 31 to 42%. CONCLUSION: Coupling of the actuator to the short process of the incus is a safe and clinically promising procedure in cases where the standard application to the long process is not feasible. In pure conductive hearing loss the benefit is comparable to long incus process coupling, whereas in mixed hearing loss slightly worse results were observed.

Cochlear Implantation in Children With Congenital Single-Sided Deafness.

OBJECTIVE: To determine audiological and clinical results of cochlear implantation in children with congenital single sided deafness (SSD), with an emphasis on children implanted before and after 6 years of age. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. SUBJECTS: Twenty one children with congenital SSD who were implanted aged 10 months to 11;3 years. INTERVENTION: Unilateral cochlear implantation. MAIN OUTCOME MEASURES: Speech recognition in noise via the German Oldenburg Sentence Test for Children (OlKiSa), lateralization ability, and subjective evaluation of hearing results using self- and third-party assessment questionnaires. RESULTS: Significant improvements of all three aspects of true binaural hearing were found. The most striking improvement was the combined head shadow effect by 2.11 dB (squelch effect: 0.95 dB, summation effect 0.98 dB). An improvement of lateralization ability was also demonstrated. Parents had a high overall level of satisfaction with their children's cochlear implantation. Subjective benefit was verified in all three subscales of the Speech, Spatial, and Qualities of Hearing Questionnaire. No significant difference was found between subjects implanted before the age of 6 with those implanted later. Three of the five subjects with a follow-up of greater than 3 years were limited users or nonusers. CONCLUSIONS: Cochlear implant (CI) provision provides children with congenital SSD with significant audiological and subjective benefits which can be seen even in children implanted after the age of 3;6. The problem of limited use and nonuser, however, should not be ignored and has to be considered for further studies.

Cry melody in 2-month-old infants with and without clefts.

OBJECTIVE: To investigate cry melody properties in infants with clefts using objective methods and to identify early differences in cry development in relation to infants without clefts that may indicate special developmental risks. DESIGN: Melody analysis was carried out on cries from the second month of life. The cry properties of infants with a cleft lip and palate (CLP) and infants with a cleft palate only (CP) were quantitatively compared. Both groups were compared to infants without clefts. PARTICIPANTS: Twenty-one infants with nonsyndromic clefts, including 11 infants with CLP and 10 infants with CP, were compared to 50 healthy controls. MAIN OUTCOME MEASURES: Frequency spectrograms and melody diagrams of about 7000 cries were analyzed. For each infant's crying, melodic and rhythmic properties were investigated and expressed by appropriate quantitative indices. Based on previous studies, the degree of melody complexity in an infants' crying was used as an indicator of their present prespeech developmental status. RESULTS: The cleft groups did not significantly differ from each other with respect to their cry melody development. However, both groups were significantly different from the control group, exhibiting a lower proportion of complex cry melodies and a deviation in rhythmicity. No significant correlation to hearing performances was found that could explain the differences. CONCLUSIONS: Infants with clefts differ in their cry development from infants without clefts at 2 months of life. This early difference occurs before the infants undergo any surgical intervention or other treatment.

CpG island promoter hypermethylation of the pro-apoptotic gene caspase-8 is a common hallmark of relapsed glioblastoma multiforme.

Glioblastoma multiforme (GBM) is an incurable malignancy with inherent tendency to recur. In this study, we have comparatively analyzed the epigenetic profile of 32 paired tumor samples of relapsed GBM and their corresponding primary neoplasms with special attention to genes involved in the mitochondria-independent apoptotic pathway. The CpG island promoter hypermethylation status was assessed by methylation-specific polymerase chain reaction and selected samples were double checked by bisulfite genomic sequencing. Thirteen genes were analyzed for DNA methylation: the pro-apoptotic CASP8, CASP3, CASP9, DcR1, DR4, DR5 and TMS1; the cell adherence CDH1 and CDH13; the candidate tumor suppressor RASSF1A and BLU; the cell cycle regulator CHFR and the DNA repair MGMT. The CpG island promoter hypermethylation profile of relapsed GBM in comparison with their corresponding primary tumors was identical in 37.5% of the cases, whereas in 62.5% of patients, differences in the DNA methylation patterns of the 13 genes were observed. The most prominent distinction was the presence of previously undetected CASP8 hypermethylation in the GBM relapses (P = 0.031). This finding was also linked to the observation that an unmethylated CASP8 CpG island together with methylated BLU promoter in the primary GBM was associated with prolonged time to tumor progression (P = 0.0035). Our data strongly suggest that hypermethylation of the pro-apoptotic CASP8 is a differential feature of GBM relapses. These remarkable findings may foster the development of therapeutic approaches using DNA demethylating drugs and activators of the extrinsic apoptotic pathway to improve the dismal prognosis of GBM.