Concomitant Obstructive Sleep Apnoea in Patients with Meniere's Disease: A Case Report and Literature Review.

Meniere's disease (MD) is a condition characterised by fluctuating and progressive hearing loss, aural fullness, tinnitus, and intermittent attacks of vertigo. The disabling vertigo symptoms can be controlled in most patients by lifestyle changes and medications such as diuretics. Should standard medical therapy fail, the patient may require surgery in order to control the disease, but such surgical procedures can be functionally destructive. Obstructive sleep apnoea syndrome (OSAS) is common, especially in people who are grossly overweight. Up to 15% of patients with MD may have concomitant OSA. Unless the OSA is well controlled, such patients may continue to experience MD symptoms despite receiving adequate standard medical therapy for MD. Moreover, MD patients may experience insomnia as a result of vertigo and/or tinnitus where sedatives are indicated. The use of sedatives with muscle relaxant properties may inadvertently further aggravate OSA resulting in a vicious cycle of symptoms. Symptoms suggestive of concomitant OSA must be proactively sought as these patients do not necessarily exhibit the obvious phenotypic features of OSA. This is especially so in Asians where OSAS is commonly observed in people who are not overly obese. We report a case of a female patient who presented with recalcitrant MD disease and was later found to have concomitant OSA. The relevant literature will be reviewed, and learning points will be discussed from the perspective of the otologist/neurotologist. The clinician must always be mindful of the existence of concomitant "silent" OSAS as this impacts the management of patients with MD.

Accidental Explantation of a Cochlear Implant in a Child Who Developed Cholesteatoma as a Late Complication of Cochlear Implantation.

INTRODUCTION: Although rare, cholesteatoma can develop as a late complication of cochlear implantation. The electrode array may then be exposed in the external auditory canal surrounded by cholesteatoma debris. Case Report. The cochlear implant of a child was inadvertently explanted by a clinician during a routine aural toilet procedure. The child had previously reported recurrent ear infections, pain, and unexplained implant function degradation. Reimplantation was carried out 2 days later with good postoperative hearing results. Part of the electrode array was observed to be embedded in cholesteatoma. Postreimplantation recovery was complicated by a breakdown of the blind-sac. Discussion. Clinical indicators that could alert the clinician to the possibility of this late complication include recurrent infections, presence of keratotic debris in the external auditory canal, unexplained implant function degradation, and nonauditory stimulation. Although this patient managed to achieve excellent postreimplantation hearing outcomes, a delay in reimplantation surgery following explantation could possibly compromise successful reinsertion of the electrode array. External ear canal overclosure without mastoid cavity obliteration has merit in facilitating CT scan surveillance, but it may increase the risk of the blind-sac breaking down. This case also illustrated how the electrode array could have facilitated propagation of the cholesteatoma from the middle ear to the mastoid. CONCLUSION: If aural toilet is required in the implanted ear of a cochlear implant recipient, any complaint of hearing change, pain, or discharge should alert the clinician of the possibility of cholesteatoma developing. It warrants prompt evaluation by an experienced otologist in order to prevent accidental explantation. Keywords. Cochlear implant, cochlear implant complications, chronic suppurative otitis media, cholesteatoma, reimplantation, blind-sac, external auditory canal overclosure, mastoid cavity obliteration.

Synergistic Ototoxicity of Gentamicin and Low-Dose Irradiation: Molecular Basis and Clinical Significance.

BACKGROUND: Inner ear structures may be included in the radiation fields when irradiation is used to treat patients with head and neck cancers. These patients may also have concurrent infections that require gentamicin treatment. Radiation and gentamicin are both potentially ototoxic, and their combined use has been shown to result in synergistic ototoxicity in animals. OBJECTIVE: We aimed to confirm the synergistic ototoxicity of combined gentamicin and low-dose irradiation treatment and identify the underlying molecular mechanisms using an in vitro model. METHOD: We compared the ototoxic effects of gentamicin, low-dose irradiation, and their combination in the OC-k3 mouse cochlear cell line using cell viability assay, live/dead stain, apoptosis detection assay, oxidative stress detection, and studied the molecular mechanisms involved using immunoblot analysis. RESULTS: Combined treatment led to prolonged oxidative stress, reduced cell viability, and synergistic apoptosis. Gentamicin induced the concurrent accumulation of LC3b-II and SQSTM1/p62, suggesting an impairment of autophagic flux. Low-dose irradiation induced transient p53 phosphorylation and persistent Akt phosphorylation in response to DNA damage. In combined treatment, gentamicin attenuated irradiation-induced Akt activation. CONCLUSIONS: Besides increased oxidative stress, synergistic apoptosis observed in combined treatment could be attributed to gentamicin-induced perturbation of autophagic flux and attenuation of Akt phosphorylation, which led to an impairment of radiation-induced DNA repair response.

An unusual case of post-cochlear implant performance degradation in a patient with suspected Cogan's syndrome.

Cogan's Syndrome is an autoimmune disorder that can affect the ear, eye and other organs. Although rare, Cogan's Syndrome is particularly relevant to the cochlear implant surgeon because the resulting hearing loss is often bilateral and the majority of cases progresses to profound levels where cochlear implantation may be indicated. There are many issues relating to this condition that concern the cochlear implant surgeon. Its rarity, lack of specific laboratory diagnostic tests and variability in the onset and types of manifestation relating to the ear, eye and other organs often pose diagnostic difficulties. Pre-operatively, the cochlear implant surgeon must anticipate and exclude the possibility of cochlear luminal obliteration and ossification. Although the post-implant hearing results are expected to be generally good in Cogan's Syndrome, the possibility of adverse hearing outcomes cannot be ruled out whether in the initial or subsequent post-operative period. The possible side effects of long-term immuno-suppressive therapy on the well-being of the cochlear implant are to be appreciated and managed. A case which posed much difficulty in management is presented and discussed to highlight some of these challenges.

Skull Base Osteomyelitis from Otitis Media Presenting as the Collet-Sicard Syndrome.

Skull base osteomyelitis can involve the jugular foramen and its associated cranial nerves resulting in specific clinical syndromes. The Collet-Sicard syndrome describes the clinical manifestations of palsies involving cranial nerves IX, X, XI, and XII. We present a rare atypical case of skull base osteomyelitis originating from infection of the middle ear and causing the Collet-Sicard syndrome. Caused by Pseudomonas aeruginosa and Klebsiella pneumoniae, this occurred in an elderly diabetic man subsequent to retention of a cotton swab in an ear with chronic suppurative otitis media. This case report illustrates the possibility of retained cotton swabs contributing to the development of otitis media, skull base osteomyelitis, and ultimately the Collet-Sicard syndrome in the ears of immune-compromised patients with chronically perforated eardrums.

Is Electroacupuncture Treatment More Effective in Somatic Tinnitus Than in Nonsomatic Tinnitus?

Background: In recent years, evidence has been accumulating linking subjective tinnitus to the somatosensory system. Somatic tinnitus is defined as tinnitus in which forceful contractions of jaw and neck muscles modulate the psychoacoustic attributes of tinnitus, such as pitch and loudness. Being a somatosensory-based treatment modality, needling might well be more effective for treating somatic than nonsomatic tinnitus. Objective: The aim of this study was to compare the outcomes of electroacupuncture (EA) treatment between patients with somatic and nonsomatic tinnitus. Materials and Methods: A single-blinded prospective study was carried wherein 27 patients with tinnitus were divided into either a somatic or a nonsomatic group, based on whether their tinnitus could be modulated by at least one of a series of forceful jaw and neck muscular contraction maneuvers. Tinnitus responses were evaluated after a single session of EA on selected acupoints for 30 minutes. Results: Seventeen of the 27 patients (63.0%) studied were found to have somatic tinnitus. Generalized estimating equation model analysis did not find any overall statistically significant difference in EA response between patients with somatic and nonsomatic tinnitus. However, patients with somatic tinnitus who were consistent in their responses to the muscular contraction maneuvers were more likely to improve with EA than variable responders to these maneuvers (62.5% versus 22.0%). Conclusions: EA did not provide increased benefits for patients with somatic tinnitus, compared to those with nonsomatic tinnitus overall. However, within the somatic tinnitus group, a subpopulation of patients appeared to be relatively more responsive to EA treatment.

Electrode array extrusion through the posterior canal wall presenting as a delayed post-cochlear implant complication.

UNLABELLED: OBJECTIVES AND IMPORTANCE: Cochlear implantation is an established, reliable, and safe procedure with a low complication rate. Electrode array extrusion through the posterior aspect of external ear canal is a potential major complication of cochlear implant surgery that may result in revision surgery or explantation. Although there have been previous case reports of such extrusions through the tympanic membrane, this is the first well-documented report of an extrusion through the posterior canal wall which was previously intact. CLINICAL PRESENTATION: In this case report, we present a case of electrode array extruding through an initially intact posterior canal wall presenting as a delayed post-operative complication in a 13-year old Asian boy. INTERVENTION: With reference to existing relevant literature, the case is discussed focusing on its management, possible contributing factors, and prevention strategies. CONCLUSION: Excessive thinning of the bony wall should be avoided as it can potentially break down. Abutment on the posterior canal wall by a coiled electrode array in the mastoid cavity exerting undue pressure on the bony wall can further contribute to additional stress. The implant surgeon must be cognizant of mastoid growth patterns in children. Life-long regular follow-up in implanted patients is crucial.

Relationship between leisure noise exposure and otoacoustic emissions in a young Asian population.

OBJECTIVE: This study compared the otoacoustic emissions amplitudes of Asian youths at risk of leisure noise exposure through the use of portable music players with their less exposed counterparts. DESIGN: A listening habit survey was conducted. Subjects were divided into two groups for analysis. A subject was placed within the high risk group if he/she reported listening to music at near maximum volume and had a physical measurement of his/her preferred listening level recorded at > 85 dBA. DPOAE and TEOAE levels were measured and compared between the two groups. STUDY SAMPLE: A total of 1928 students from a tertiary educational institution in Singapore. RESULTS: TEOAE levels were found to be significantly lower in the high risk group at 4 kHz. DPOAE levels were also found to be significantly depressed in the high risk group at 1, 2, 3, and 4 kHz with the largest mean difference at 4 kHz. A four-way ANOVA carried out for OAE amplitudes using gender, ear laterality, risk profile, and years of usage as independent factors also showed that risk profile was a significant factor in determining the OAE amplitude at 4 kHz. CONCLUSION: We have demonstrated that both DPAOE and TEOAE values are diminished in the Asian subjects at high risk for noise exposure.

The music listening preferences and habits of youths in Singapore and its relation to leisure noise-induced hearing loss.

INTRODUCTION: Noise-induced hearing loss (NIHL) is a preventable condition, and much has been done to protect workers from it. However, thus far, little attention has been given to leisure NIHL. The purpose of this study is to determine the possible music listening preferences and habits among young people in Singapore that may put them at risk of developing leisure NIHL. METHODS: In our study, the proportion of participants exposed to > 85 dBA for eight hours a day (time-weighted average) was calculated by taking into account the daily number of hours spent listening to music and by determining the average sound pressure level at which music was listened to. RESULTS: A total of 1,928 students were recruited from Temasek Polytechnic, Singapore. Of which, 16.4% of participants listened to portable music players with a time-weighted average of > 85 dBA for 8 hours. On average, we found that male students were more likely to listen to music at louder volumes than female students (p < 0.001). We also found that the Malay students in our study listened to louder music than the Chinese students (p < 0.001). CONCLUSION: We found that up to one in six young persons in Singapore is at risk of developing leisure NIHL from music delivered via earphones. As additional risks due to exposure to leisure noise from other sources was not taken into account, the extent of the problem of leisure NIHL may be even greater. There is a compelling need for an effective leisure noise prevention program among young people in Singapore.

Management of major post-cochlear implant wound infections.

In post-cochlear implant (CI) wound infections, a commonly asked question is whether the device could be salvaged and if so, what the challenges were. The aim of this article is to study patients with major post-CI wound infections, identify the risk factors and discuss the management. The case records all CI recipients who developed post-CI wound infections that required parenteral antibiotics treatment or any form of surgery between Jan 1997 and Dec 2011 were retrospectively reviewed. Among the 432 CI surgeries performed by the senior author, 7 developed major post-CI wound infection (1.62 %). In children, the commonest etiology was from stitch abscesses. In four out of the five children who developed stitch abscesses, four were due to the use of non-absorbable polypropylene sutures, a technique which had since been discontinued. In adults, the cause was due to the late effects of prior radiotherapy for head and neck tumors. The commonest organism isolated from wound cultures was Staphylococcus aureus. Salvage surgery (complemented by antibiotics) was attempted in six out of eight patients managed. All were successfully salvaged with surgery entailing either skin flap reconstruction (2 patients), transposition of the CI body to new location (1 patient) or both (3 patients). Skin flap reconstruction surgery alone failed to control the infection in patients with a negative culture result and needed a subsequent transposition surgery of the device. Device transposition surgery was a consistently effective therapeutic approach, but carried a higher risk of iatrogenic damage to the electrode array as it might be embedded in new bone.

Cochlear Implant Outcomes: A Comparison between Irradiated and Non-irradiated Ears.

OBJECTIVES: Radiotherapy for head and neck tumors is known to potentially induce sensorineural hearing loss, which is possibly due to damage to the cochlear and/or auditory pathways. Since the success of cochlear implantation depends on a functional auditory nerve, this paper aims to study the hearing outcomes of cochlear implantation in irradiated ears. METHODS: A retrospective study of cochlear implant recipients from our institution who had previously received radiotherapy for head and neck cancers was performed. A control group with cochlear implants who did not receive radiotherapy was recruited. A review of case records, speech discrimination scores (SDS), and a validated subjective questionnaire in the form of the Abbreviated Profile of Hearing Aid Benefit (APHAB) was administered to the study group who fulfilled the inclusion criteria. Global and category scores in both groups were averaged and statistically compared via non-inferiority (NI) testing. RESULTS: With the control group (n=8) as the reference, the -ΔNI was defined, and a one-tailed lower 95% confidence interval was used for the irradiated group (n=8). The APHAB degree of improvement (%) results were as follows: global, 28.9% (19.32%, -ΔNI=16.3%); ease of communication, 67.0% (58.36%, -ΔNI=37.5%); background noise, 53.2% (44.14%, -ΔNI=26.8%); reverberation, 41.7% (28.85%, -ΔNI=32.7%); and aversiveness, -46.2% (-67.80%, -ΔNI=-56.9%). The SDS was 66.9% (56.02%, -ΔNI=51.0%). From the results, lower 95% confidence interval limits of global APHAB, SDS, ease of communication, and background noise scores of the irradiated group were within the defined -ΔNI boundary and hence are not inferior to the control. The categories of reverberation and aversiveness could not be proven, however. CONCLUSION: This study demonstrated marked improvements in hearing measured both objectively and subjectively. The overall hearing outcomes after cochlear implantation for post-irradiated patients were not worse than patients who have had no prior irradiation to ear structures.

Acoustic brainstem implant in a post-meningitis deafened child-Lessons learned.

We report a case of a deafened child with advanced labyrinthitis ossificans resulting from meningo-encephalitis. She received a cochlear implant in the right ear, following a drill-out procedure. Post-implant hearing outcomes were satisfactory initially, but deteriorated over time as a result of partial electrode migration. The child subsequently received a left auditory brainstem implantation with improvement of hearing outcomes. Post-operatively, a sub-dural hematoma developed not on the side of the operation but on the opposite side. Simultaneous use of the cochlear implant on one side and the acoustic brainstem on the other, aggravated the non-auditory side effects of the ABI and compromised its potential for optimal hearing results.

Ototoxicity from combined Cisplatin and radiation treatment: an in vitro study.

Objective. Combined cisplatin (CDDP) and radiotherapy is increasingly being used to treat advanced head and neck cancers. As both CDDP and radiation can cause hearing loss, it is important to have a better understanding of the cellular and molecular ototoxic mechanisms involved in combined therapy. Procedure. The effects of CDDP, radiation, and combined CDDP-radiation on the OC-k3 cochlear cell line were studied using MTS assay, flow cytometry, Western blotting, and microarray analysis. Results. Compared to using CDDP or radiation alone, its combined use resulted in enhanced apoptotic cell death and apoptotic-related gene expression, including that of FAS. Phosphorylation of p53 at Ser15 (a marker for p53 pathway activation in response to DNA damage) was observed after treatment with either CDDP or radiation. However, posttreatment activation of p53 occurred earlier in radiation than in CDDP which corresponded to the timings of MDM2 and TP53INP1 expression. Conclusion. Enhanced apoptotic-related gene expressions leading to increased apoptotic cell deaths could explain the synergistic ototoxicity seen clinically in combined CDDP-radiation therapy. CDDP and radiation led to differential temporal activation of p53 which suggests that their activation is the result of different upstream processes. These have implications in future antiapoptotic treatments for ototoxicity.

12th Yahya Cohen Memorial Lecture: The cellular and molecular basis of radiation-induced sensori-neural hearing loss.

INTRODUCTION: Sensori-neural hearing loss (SNHL) is a frequent complication of conventional radiotherapy for head and neck tumours, especially nasopharyngeal carcinoma. To manage radiation-induced ototoxicity appropriately, an understanding of the cellular and molecular basis of this complication is necessary. MATERIALS AND METHODS: A medline search of relevant literature was done, focusing on the radiation-induced cellular and molecular processes that lead to hair cell death in the cochlea. RESULTS: Radiation-induced SNHL occurs in the cochlea, with the retro-cochlear pathways remaining functionally intact. By simulating radiotherapy regimes used clinically, radiation-induced cochlear cell degeneration in the absence of damage to the supporting structures and blood vessels has been demonstrated in animals. This could be due to apoptotic cochlear cell death, which has been shown to be associated with p53 upregulation and intra-cellular reactive oxygen species (ROS) generation. Oxidative stress may initiate the upstream processes that lead to apoptosis and other cell death mechanisms. CONCLUSIONS: A model of radiation-induced SNHL based on a dose and ROS-dependent cochlear cell apoptosis, is proposed. This model supports the feasibility of cochlear implantation, should one be clinically indicated. It can explain clinical observations such as radiation-induced SNHL being dose-dependent and affects the high frequencies more than the lower frequencies. It also opens up the possibility of preventive strategies targeted at different stages of the apoptotic process. Antioxidants look promising as effective agents to prevent radiation-induced ototoxicity; they target upstream processes leading to different cell death mechanisms that may co-exist in the population of damaged cells.

Association of Epstein-Barr virus with nasopharyngeal carcinoma and current status of development of cancer-derived cell lines.

It is well known that the Epstein-Barr virus (EBV) contributes directly to tumourigenesis in nasopharyngeal carcinoma (NPC), primarily in the undifferentiated form of NPC (WHO type III; UNPC or UC), which is commonly found in South East Asia. Unfortunately, research in NPC has been severely hampered by the lack of authentic EBV-positive (EBV+) human NPC cell lines for study. Since 1975, there have been more than 20 reported NPC cell lines. However, many of these NPC-derived cell lines do not express EBV transcripts in long-term culture, and therefore that finding may dispute the fundamental theory of NPC carcinogenesis. In fact, currently only one EBV+ human NPC cell line (C-666) in long-term culture has been reported. Hence, most of the NPC cell lines may not be representative of the disease itself. In order to better understand and treat NPC, there is an urgent need to develop more EBV+ human NPC cell lines. In this review, we discuss the authenticity of existing NPC cell lines and the impact of our understanding of NPC biology on the treatment of the disease and the relationship of EBV to NPC in the context of cell lines.

L-N-Acetylcysteine protects against radiation-induced apoptosis in a cochlear cell line.

CONCLUSION: L-N-Acetylcysteine (L-NAC) significantly reduced reactive oxygen species (ROS) generation and cochlear cell apoptosis after irradiation. The safe and effective use of L-NAC in reducing radiation-induced sensorineural hearing loss (SNHL) should be verified by further in vivo studies. OBJECTIVES: Radiation-induced SNHL is a common complication after radiotherapy of head and neck tumours. There is growing evidence to suggest that ROS play an important role in apoptotic cochlear cell death from ototoxicity, resulting in SNHL. The aim of this study was to evaluate the effectiveness of L-NAC, an antioxidant, on radiation-induced apoptosis in cochlear cells. MATERIALS AND METHODS: The OC-k3 cochlear cell line was studied after 0 and 20 Gy of gamma-irradiation. Cell viability assay was performed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide. Flow cytometry and TUNEL assay were done with and without the addition of 10 mmol/L of L-NAC. Intracellular generation of ROS was detected by 2',7'-dichlorofluorescein diacetate, with comparisons made using fluorescence intensity. RESULTS: L-NAC increased the viability of cells after irradiation. Generation of ROS was demonstrated at 1 h post-irradiation and was significantly reduced by L-NAC (p<0.0001). Flow cytometry and TUNEL assay showed cell apoptosis at 72 h post-irradiation, which was diminished by the addition of L-NAC.

Outcome of early cochlear implantation.

INTRODUCTION: Universal newborn hearing screening facilitates early detection of congenital hearing loss. A child found to have severe to profound hearing loss may require a cochlear implant to access sounds in the speech frequency range. MATERIALS AND METHODS: This retrospective study compared the speech perception outcomes of children implanted at 2 years and below (C1) with those implanted later (C3). Baseline and post-implant speech perception scores were recorded using IT-MAIS, TACL-R or PPVT. The percentage of improvement was calculated for each group and statistical significance was determined using the Student's t-test. RESULTS: The median follow-up period for C1 (n = 29) and C3 (n = 29) was 29 months (range, 6 to 29 months) and 20 months (range, 5 to 32 months) respectively, which was not statistically significant. Although both groups recorded post-implant improvement of speech reception scores, the difference in the degrees of improvement was statistically significant (P = 0.034). CONCLUSION: More rapid development of speech perceptive skills was achieved in children who were implanted early. Early implantation therefore, enables children to develop good core listening skills and to potentially develop spoken language at a young age. This enhances successful integration into mainstream pre-schools which provide the environment for the early nurturing of social and cognitive skills.

Preauricular sinus: clinical course and associations.

OBJECTIVES: To evaluate the clinical course of congenital preauricular sinus (PAS) up until adulthood and to determine its association with congenital ear and renal abnormalities. DESIGN: Cohort survey. SETTING: Medical screening facility at a military base. PARTICIPANTS: All individuals in a cohort of male subjects who were medically assessed for conscription into the army between September 1, 2003, and March 31, 2004. INTERVENTIONS: Subjects identified as having PAS were further evaluated with pure-tone audiometry and renal ultrasonography. MAIN OUTCOME MEASURES: Presence of PAS and associated hearing and renal abnormalities. RESULTS: Of 10 734 male subjects (median age, 19 years; range, 16-26 years) screened, 121 (1.13%) were found to have PAS, all of which were isolated. The point prevalence of PAS in Chinese, Malay, and Indian subjects was 1.36%, 0.69%, and 0.17%, respectively. Of the 29 subjects (24.0%) who developed symptoms (mainly sinus discharge), most had recurrent symptoms, and 7 (24.1%) of the 29 had onset of symptoms after age 16 years. Only 1.7% and 2.6% of the subjects had associated hearing loss (sensorineural) and renal deformity (minor in nature), respectively. CONCLUSIONS: In a study of young adult males with PAS, associations with ear and renal abnormalities were found to be rare, although PAS had widely been acknowledged to be associated with these congenital defects. Up until adulthood, about one quarter of all lesions became symptomatic. Of those who developed symptoms, almost one third did so after age 16 years. The most common symptom was sinus discharge, which tended to be recurrent.