A deafness mechanism of digenic Cx26 (GJB2) and Cx30 (GJB6) mutations: Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wall.

Digenic Connexin26 (Cx26, GJB2) and Cx30 (GJB6) heterozygous mutations are the second most frequent cause of recessive deafness in humans. However, the underlying deafness mechanism remains unclear. In this study, we created different double Cx26 and Cx30 heterozygous (Cx26+/-/Cx30+/-) mouse models to investigate the underlying pathological changes and deafness mechanism. We found that double Cx26+/-/Cx30+/- heterozygous mice had hearing loss. Endocochlear potential (EP), which is a driving force for hair cells producing auditory receptor current, was reduced. However, unlike Cx26 homozygous knockout (Cx26-/-) mice, the cochlea in Cx26+/-/Cx30+/- mice displayed normal development and had no apparent hair cell degeneration. Gap junctions (GJs) in the cochlea form two independent networks: the epithelial cell GJ network in the organ of Corti and the connective tissue GJ network in the cochlear lateral wall. We further found that double heterozygous deletion of Cx26 and Cx30 in the epithelial cells did not reduce EP and had normal hearing, suggesting that Cx26+/-/Cx30+/- may mainly impair gap junctional functions in the cochlear lateral wall and lead to EP reduction and hearing loss. Most of Cx26 and Cx30 in the cochlear lateral wall co-expressed in the same gap junctional plaques. Moreover, sole Cx26+/- or Cx30+/- heterozygous mice had no hearing loss. These data further suggest that digenic Cx26 and Cx30 mutations may impair heterozygous coupling of Cx26 and Cx30 in the cochlear lateral wall to reduce EP, thereby leading to hearing loss.

Adult progressive sensorineural hearing loss: is preoperative imaging necessary before cochlear implantation?

OBJECTIVE: Preoperative evaluation of cochlear implant candidate includes routine imaging to identify anatomic abnormalities that may preclude or complicate implantation, such as cochlear aplasia, absent/narrowed internal auditory canals, cochlear ossificans, or significant traumatic fracture. The aim of this study is to determine if preoperative imaging is necessary in select cochlear implant candidates, thus defraying cost and ionizing radiation. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral facility. PATIENTS: Adult patients with progressive sensorineural hearing loss without evidence of head trauma, meningitis, or congenital hearing loss who underwent cochlear implantation. INTERVENTIONS: Diagnostic and therapeutic. MAIN OUTCOME MEASURES: Preoperative radiologic abnormalities, deviation from standard cochlear implant operation. RESULTS: One hundred eighteen cochlear implants met inclusion criteria; 23.7% of CT scans had a documented abnormality, including chronic otitis media (14.4%), otosclerosis (4.2%), and an enlarged vestibular aqueduct (3.4%). There were 6 eventful surgeries in patients with normal documented CT scan. Events included multiple insertion attempts (3.4%), CSF leak (2.5%), and no apparent round window (2.5%). In every case, a cochlear implant was able to be placed successfully. CONCLUSION: In the appropriately selected patient, preoperative imaging is not necessary as it does not impact the cochlear implant surgery and will defray cost and ionizing radiation.

Hot or cold? Is monothermal caloric testing useful and cost-effective?

OBJECTIVES: Videonystagmography (VNG) is used widely in the assessment of balance dysfunction. The full test battery can be time-consuming and can induce patient discomfort. The purpose of this study was to examine the value of monothermal caloric testing in predicting unilateral caloric weakness, as well as abnormal VNG vestibular and nonvestibular eye movement, while considering the time and reimbursement associated with these tests. METHODS: In a retrospective review of 645 patients who completed a comprehensive VNG test battery with bithermal caloric testing, we calculated the specificity, sensitivity, and predictive values of monothermal caloric testing in relation to bithermal caloric results and noncaloric VNG results. RESULTS: With unilateral vestibular weakness (UVW) defined as a 25% interear difference, warm-air monothermal caloric testing yielded a sensitivity of 87% and a negative predictive value of 90% for predicting UVW. With a 10% UVW definition, the warm-air caloric testing sensitivity increased to 95% and the negative predictive value to 92%. Warm-air monothermal caloric testing had a positive predictive value of 85% and a negative predictive value of 18% for predicting noncaloric VNG findings; cold-air monothermal and bithermal testing displayed similar results. CONCLUSIONS: Isolated monothermal testing is a sensitive screening tool for detecting UVW, but is not adequate for predicting noncaloric VNG results.

The effects and outcomes of electrolyte disturbances and asphyxia on newborns hearing.

OBJECTIVE: To determine the effect of electrolyte disturbances (ED) and asphyxia on infant hearing and hearing outcomes. STUDY DESIGN: We conducted newborn hearing screening with transient evoked otoacoustic emission (TEOAE) test on a large scale (>5000 infants). The effects of ED and asphyxia on infant hearing and hearing outcomes were evaluated. RESULT: The pass rate of TEOAE test was significantly reduced in preterm infants with ED (83.1%, multiple logistic regression analysis: P<0.01) but not in full-term infants with ED (93.6%, P=0.41). However, there was no significant reduction in the pass rate in infants with asphyxia (P=0.85). We further found that hypocalcaemia significantly reduced the pass rate of TEOAE test (86.8%, P<0.01). In the follow-up recheck at 3 months of age, the pass rate remained low (44.4%, P<0.01). CONCLUSION: ED is a high-risk factor for preterm infant hearing. Hypocalcaemia can produce more significant impairment with a low recovery rate.

The clinical reliability of vestibular evoked myogenic potentials.

Vestibular evoked myogenic potential (VEMP) testing has gained popularity as a diagnostic modality in otolaryngology and audiology. To maximize the utility of this test, examiners need the availability of ideal test settings and reliable norms. We conducted a prospective study of 8 subjects with no history of neurotologic symptoms to examine the test-retest consistency of VEMP testing and to analyze the impact of stimulus type and muscle tension monitoring. All subjects underwent VEMP testing with two stimuli: a 500-Hz tone and a click. With each stimulus, testing was completed with and without monitoring of sternocleidomastoid muscle tension. All subjects participated in an initial testing session and then returned for a repeat testing session 2 to 4 weeks later. We measured the amplitude of primary waveforms P13 (first positive peak) and N23 (first negative peak) and analyzed the reliability and reproducibility of the mean amplitude asymmetry of these VEMP peaks. The P13 component of the VEMP (specificity: 86.25%) demonstrated a more stable amplitude than did the N23 component (specificity: 70.50%). Therefore, our statistical analysis of the effect of stimulus type and muscle tension monitoring on test-retest reliability was limited to the P13 waveform. We found that neither the type of stimulus nor the presence or absence of muscle tension monitoring had any statistically significant effect on amplitude asymmetry. We concluded that in VEMP testing, the P13 component was more specific than the N23 component in identifying normal subjects and that the P13 component provided consistent results across test sessions, regardless of the type of stimulus or the presence or absence of muscle tension monitoring.

Correlation of central auditory processing deficits and vascular loop syndrome.

We report a case involving a 49-year-old woman with vascular loop syndrome. The patient was evaluated because of complaints of decreased hearing sensitivity in her right ear. Central auditory tests were performed. The patient was found to have an asymmetry on pure-tone audiometry and an auditory processing deficit, suggesting central pathology. Magnetic resonance imaging confirmed central involvement, revealing a vascular loop extending into the right internal auditory canal. This case report demonstrates that auditory deficits may result from vascular loop compression and that these deficits may benefit from a battery of tests to help identify and localize the pathology.

The value of CT venography in the diagnosis of jugular bulb diverticulum: a series of 3 cases.

Jugular bulb diverticulum is a rare diagnosis, as fewer than 50 cases have been reported in the literature. It has been reported that unilateral auditory symptoms may accompany this entity, although some patients are asymptomatic. We present a case series of 3 patients who were referred to our tertiary care neurotology center with a unilateral jugular bulb diverticulum along with unilateral sensorineural hearing loss and tinnitus. These patients were evaluated clinically and radiographically. This case series (1) adds further documentation of the presence of unilateral auditory symptoms in patients with a jugular bulb diverticulum and (2) demonstrates the value of computed tomographic venography in the diagnosis of jugular bulb diverticulum.

Auditory brainstem response threshold differences in patients with vestibular schwannoma: a new diagnostic index.

Auditory brainstem response (ABR) testing is less sensitive in detecting small vestibular schwannomas than medium-size tumors. Magnetic resonance imaging (MRI) is more sensitive than ABR alone for small and large tumors, but it carries with it increased cost and issues of unavailability and patient discomfort. We conducted a prospective pilot study of 7 patients with untreated MRI-proven, unilateral vestibular schwannoma to determine if we could increase the sensitivity of ABR testing in detecting small tumors. Our method involved the use of a new ABR index that is based on threshold differences. All patients underwent pure-tone audiometry followed by a determination of behavioral threshold and neurodiagnostic threshold ABR in the normal ear, which was used as a control, and in the diseased ear. Analysis of results revealed that all 7 patients had an abnormal ABR threshold difference, and 5 patients displayed abnormal traditional ABR indices. The mean difference between the ABR and behavioral click thresholds was 41.4 dB in the diseased ears (with the ABR threshold being higher than the click threshold) and 15.8 dB in the normal ears. None of the control ears had a threshold difference > 30 dB.

Long-term hearing results in gamma knife radiosurgery for acoustic neuromas.

OBJECTIVES: There are many studies that have examined functional outcomes following Gamma Knife treatment; however, few have reported long-term audiometric data. This study analyzed the long-term hearing results of Gamma Knife radiosurgery in the treatment of acoustic neuromas. STUDY DESIGN: Retrospective cohort study. METHODS: Seventeen patients were selected from our acoustic neuroma Gamma Knife registry of 113 patients treated from 1991 to 2005. Pretreatment audiograms were analyzed for pure-tone average and word recognition scores and assigned a Gardner-Robertson classification score (GRC). Either a current audiogram was obtained or the most recent audiogram (if the patient was lost to follow-up) was reviewed from clinic charts and these were compared with the preoperative results. Audiometric data of the pre- and posttreatment normal ear were obtained and used as the patient's own control. RESULTS: The tumor size ranged from 0.5 to 2.8 cm (mean, 1.33 cm) and patients received a range of 12.5-16 Gy (mean, 13.82 Gy) to 50% isodose line. Patient follow-up ranged from 3 to 82 months with a mean of 33.6 months. Pretreatment pure-tone average for the involved side group was 30.6 dB HL with a word recognition score of 74%. Pretreatment mean GRC was 1.76. posttreatment pure-tone average for the group was 59.7 dB HL with a word recognition score of 37%. posttreatment mean GRC was 3.29. Comparing pre- versus post-Gamma Knife radiosurgery results on the treatment ear, means were statistically significantly different for both pure-tone average and word recognition scores, based on a paired-samples t test (P < .001 for both). The group "normal" ear pure-tone average was 14 dB HL and 17.75 dB HL pre- and posttreatment, respectively. Normal ear pre- and posttreatment word recognition score and GRC were 93% and 98%, and 1.13 and 1.31, respectively. CONCLUSION: Gamma Knife radiosurgery remains a noninvasive treatment option for patients with acoustic neuromas; however, they may experience a delayed hearing loss. Of those patients with useful audition pretreatment, 42% maintained useful hearing posttreatment.

Paradoxical enhancement of active cochlear mechanics in long-term administration of salicylate.

Aspirin (salicylate) is a common drug and frequently used long term in the clinic. It has been well documented that salicylate can cause reversible hearing loss and tinnitus and diminish outer hair cell (OHC) electromotility, which is capable of actively boosting the basilar membrane vibration and producing acoustic emission. However, aspirin's ototoxic mechanisms still remain largely unclear. In this experiment, the effects of long-term salicylate administration on cochlear hearing functions were investigated by measuring distortion product otoacoustic emissions (DPOAEs) in awake guinea pigs. A single injection of sodium salicylate (200 mg/kg) could reduce the amplitude of the cubic distortion product of 2f1-f2 within 2 h. The reduction was significant at 20-50 dB SPL stimulus levels and recovered after 8 h. However, following daily injections of sodium salicylate (200 mg/kg, b.i.d.), the distortion product of 2f1-f2 progressively increased. After injection for 14 days, the distortion product increased about 2-3.5 dB SPL. The increase rate was about 0.2 dB SPL/day. The DP-I/O function remained nonlinear. The increase was greater at 40-70 dB SPL primary sound intensities and reversible. After cessation of salicylate treatment for 4 wk, the increased distortion product returned to the initial normal levels. The rate of recovery was 0.1 dB SPL/day. In the control animals with saline injection, there was no change in DPOAEs. The data revealed that long-term administration of salicylate could paradoxically enhance active cochlear mechanics. The data also suggested that salicylate-induced tinnitus might be generated at the OHC level.

Differential ototoxicities induced by lead acetate and tetraethyl lead.

Lead poisoning disrupts many biological structures and functions, including those of the auditory system. This study examined the ototoxic effects of lead acetate (LA) and tetraethyl lead (TEL) of equal lead content on cochlear function and the ability of alpha-phenyl-tert-butyl-nitrone (PBN) to attenuate such effects. Baseline 1.0 microV cochlear microphonic (CM) and compound action potential (CAP) responses were recorded and animals administered either PBN (100 mg/kg, i.p.) or an equal volume of 0.9% saline, followed by an i.p. injection of LA (50 mg/kg) in an ethanol vehicle, TEL (42.7 mg/kg) in a corn oil vehicle, corn oil or ethanol vehicle alone. Two hours after administration, post-exposure CM and CAP responses were recorded. CAP threshold shifts in the saline-LA group were elevated by 5-10 dB at mid to high frequencies relative to controls (20-24 kHz, P<0.05). Mean CAP threshold shifts in the saline-TEL were significantly greater than those of both control groups at all tested frequencies except 2 kHz (P<0.001). However, threshold shifts in the group receiving PBN prior to TEL were significantly smaller than shifts in the group receiving saline prior to TEL (P<0.01). These data suggest that TEL is more ototoxic than is LA and that free radicals partially mediate TEL-induced CAP disruption.