Christopher F. Halpin

Oral vs Intratympanic Corticosteroid Therapy for Idiopathic Sudden Sensorineural Hearing Loss: A Randomized Trial

CONTEXTnIdiopathic sudden sensorineural hearing loss has been treated with oral corticosteroids for more than 30 years. Recently, many patients symptoms have been managed with intratympanic steroid therapy. No satisfactory comparative effectiveness study to support this practice exists.nnnOBJECTIVEnTo compare the effectiveness of oral vs intratympanic steroid to treat sudden sensorineural hearing loss.nnnDESIGN, SETTING, AND PATIENTSnProspective, randomized, noninferiority trial involving 250 patients with unilateral sensorineural hearing loss presenting within 14 days of onset of 50 dB or higher of pure tone average (PTA) hearing threshold. The study was conducted from December 2004 through October 2009 at 16 academic community-based otology practices. Participants were followed up for 6 months.nnnINTERVENTIONnOne hundred twenty-one patients received either 60 mg/d of oral prednisone for 14 days with a 5-day taper and 129 patients received 4 doses over 14 days of 40 mg/mL of methylprednisolone injected into the middle ear.nnnMAIN OUTCOME MEASURESnPrimary end point was change in hearing at 2 months after treatment. Noninferiority was defined as less than a 10-dB difference in hearing outcome between treatments.nnnRESULTSnIn the oral prednisone group, PTA improved by 30.7 dB compared with a 28.7-dB improvement in the intratympanic treatment group. Mean pure tone average at 2 months was 56.0 for the oral steroid treatment group and 57.6 dB for the intratympanic treatment group. Recovery of hearing on oral treatment at 2 months by intention-to-treat analysis was 2.0 dB greater than intratympanic treatment (95.21% upper confidence interval, 6.6 dB). Per-protocol analysis confirmed the intention-to-treat result. Thus, the hypothesis of inferiority of intratympanic methylprednisolone to oral prednisone for primary treatment of sudden sensorineural hearing loss was rejected.nnnCONCLUSIONnAmong patients with idiopathic sudden sensorineural hearing loss, hearing level 2 months after treatment showed that intratympanic treatment was not inferior to oral prednisone treatment.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00097448.

Clinical investigation and mechanism of air-bone gaps in large vestibular aqueduct syndrome.

Objectives: Patients with large vestibular aqueduct syndrome (LVAS) often demonstrate an air-bone gap at the low frequencies on audiometric testing. The mechanism causing such a gap has not been well elucidated. We investigated middle ear sound transmission in patients with LVAS, and present a hypothesis to explain the air-bone gap. Methods: Observations were made on 8 ears from 5 individuals with LVAS. The diagnosis of LVAS was made by computed tomography in all cases. Investigations included standard audiometry and measurements of umbo velocity by laser Doppler vibrometry (LDV) in all cases, as well as tympanometry, acoustic reflex testing, vestibular evoked myogenic potential (VEMP) testing, distortion product otoacoustic emission (DPOAE) testing, and middle ear exploration in some ears. Results: One ear with LVAS had anacusis. The other 7 ears demonstrated air-bone gaps at the low frequencies, with mean gaps of 51 dB at 250 Hz, 31 dB at 500 Hz, and 12 dB at 1,000 Hz. In these 7 ears with air-bone gaps, LDV showed the umbo velocity to be normal or high normal in all 7; tympanometry was normal in all 6 ears tested; acoustic reflexes were present in 3 of the 4 ears tested; VEMP responses were present in all 3 ears tested; DPOAEs were present in 1 of the 2 ears tested, and exploratory tympanotomy in 1 case showed a normal middle ear. The above data suggest that an air-bone gap in LVAS is not due to disease in the middle ear. The data are consistent with the hypothesis that a large vestibular aqueduct introduces a third mobile window into the inner ear, which can produce an air-bone gap by 1) shunting air-conducted sound away from the cochlea, thus elevating air conduction thresholds, and 2) increasing the difference in impedance between the scala vestibuli side and the scala tympani side of the cochlear partition during bone conduction testing, thus improving thresholds for bone-conducted sound. Conclusions: We conclude that LVAS can present with an air-bone gap that can mimic middle ear disease. Diagnostic testing using acoustic reflexes, VEMPs, DPOAEs, and LDV can help to identify a non?middle ear source for such a gap, thereby avoiding negative middle ear exploration. A large vestibular aqueduct may act as a third mobile window in the inner ear, resulting in an air-bone gap at low frequencies.

Dilated Cardiomyopathy and Sensorineural Hearing Loss A Heritable Syndrome That Maps to 6q23–24

BACKGROUNDnDilated cardiomyopathy (DCM) and sensorineural hearing loss (SNHL) are prevalent disorders that occur alone or as components of complex multisystem syndromes. Multiple genetic loci have been identified that, when mutated, cause DCM or SNHL. However, the isolated coinheritance of these phenotypes has not been previously recognized.nnnMETHODS AND RESULTSnClinical evaluations of 2 kindreds demonstrated autosomal-dominant transmission and age-related penetrance of both SNHL and DCM in the absence of other disorders. Moderate-to-severe hearing loss was evident by late adolescence, whereas ventricular dysfunction produced progressive congestive heart failure after the fourth decade. DNA samples from the larger kindred (29 individuals) were used to perform a genome-wide linkage study. Polymorphic loci on chromosome 6q23 to 24 were coinherited with the disease (maximum logarithm of odds score, 4.88 at locus D6S2411). The disease locus must lie within a 2.8 cM interval between loci D6S975 and D6S292, a location that overlaps an SNHL disease locus (DFNA10). However, DFNA10 does not cause cardiomyopathy. The epicardin gene, which encodes a transcription factor expressed in the myocardium and cochlea, was assessed as a candidate gene by nucleotide sequence analysis; no mutations were identified.nnnCONCLUSIONSnA syndrome of juvenile-onset SNHL and adult-onset DCM is caused by a mutation at 6q23 to 24 (locus designated CMD1J). Recognition of this cardioauditory disorder allows for the identification of young adults at risk for serious heart disease, thereby enabling early intervention. Definition of the molecular cause of this syndrome may provide new information about important cell physiology common to both the ear and heart.

COMPARISON OF EAR-CANAL REFLECTANCE AND UMBO VELOCITY IN PATIENTS WITH CONDUCTIVE HEARING LOSS: A PRELIMINARY STUDY

Objective: The goal of the present study was to investigate the clinical utility of measurements of ear-canal reflectance (ECR) in a population of patients with conductive hearing loss in the presence of an intact, healthy tympanic membrane and an aerated middle ear. We also sought to compare the diagnostic accuracy of umbo velocity (VU) measurements and measurements of ECR in the same group of patients. Design: This prospective study comprised 31 adult patients with conductive hearing loss, of which 14 had surgically confirmed stapes fixation due to otosclerosis, 6 had surgically confirmed ossicular discontinuity, and 11 had computed tomography and vestibular evoked myogenic potential confirmed superior semicircular canal dehiscence (SCD). Measurements on all 31 ears included pure-tone audiometry for 0.25 to 8 kHz, ECR for 0.2 to 6 kHz using the Mimosa Acoustics HearID system, and VU for 0.3 to 6 kHz using the HLV-1000 laser Doppler vibrometer (Polytec Inc, Waldbronn, Germany). We analyzed power reflectance |ECR|2 as well as the absorbance level = 10 × log10(1 − |ECR|2). All measurements were made before any surgical intervention. The VU and ECR data were plotted against normative data obtained in a companion study of 58 strictly defined normal ears (Rosowski et al., 2011). Results: Small increases in |ECR|2 at low-to-mid frequencies (400–1000 Hz) were observed in cases with stapes fixation, while narrowband decreases were seen for both SCD and ossicular discontinuity. The SCD and ossicular discontinuity differed in that the SCD had smaller decreases at mid-frequency (∼1000 Hz), whereas ossicular discontinuity had larger decreases at lower frequencies (500–800 Hz). SCD tended to have less air-bone gap at high frequencies (1–4 kHz) compared with stapes fixation and ossicular discontinuity. The |ECR|2 measurements, in conjunction with audiometry, could successfully separate 28 of the 31 cases into the three pathologies. By comparison, VU measurements, in conjunction with audiometry, could successfully separate various pathologies in 29 of 31 cases. Conclusions: The combination of |ECR|2 with audiometry showed clinical utility in the differential diagnosis of conductive hearing loss in the presence of an intact tympanic membrane and an aerated middle ear and seems to be of similar sensitivity and specificity to measurements of VU plus audiometry. Additional research is needed to expand upon these promising preliminary results.

Ear-canal reflectance, umbo velocity, and tympanometry in normal-hearing adults.

Objective: This study compares measurements of ear-canal reflectance (ECR) to other objective measurements of middle ear function including audiometry, umbo velocity (VU), and tympanometry in a population of strictly defined normal-hearing ears. Design: Data were prospectively gathered from 58 ears of 29 normal-hearing subjects, 16 females and 13 males, aged 22 to 64 yr. Subjects met all of the following criteria to be considered as having normal hearing: (1) no history of significant middle ear disease; (2) no history of otologic surgery; (3) normal tympanic membrane on otoscopy; (4) pure-tone audiometric thresholds of 20 dB HL or better for 0.25 to 8 kHz; (5) air-bone gaps no greater than 15 dB at 0.25 kHz and 10 dB for 0.5 to 4 kHz; (6) normal, type-A peaked tympanograms; and (7) all subjects had two “normal” ears (as defined by these criteria). Measurements included pure-tone audiometry for 0.25 to 8 kHz, standard 226 Hz tympanometry, ECR for 0.2 to 6 kHz at 60 dB SPL using the Mimosa Acoustics HearID system, and umbo velocity (VU) for 0.3 to 6 kHz at 70 to 90 dB SPL using the HLV-1000 laser Doppler vibrometer (Polytec Inc). Results: Mean power reflectance (|ECR|2) was near 1.0 at 0.2 to 0.3 kHz, decreased to a broad minimum of 0.3 to 0.4 between 1 and 4 kHz, and then sharply increased to almost 0.8 by 6 kHz. The mean pressure reflectance phase angle (∠ECR) plotted on a linear frequency scale showed a group delay of approximately 0.1 msec for 0.2 to 6 kHz. Small significant differences were observed in |ECR|2 at the lowest frequencies between right and left ears and between males and females at 4 kHz. |ECR|2 decreased with age but reached significance only at 1 kHz. Our ECR measurements were generally similar to previous published reports. Highly significant negative correlations were found between |ECR|2 and VU for frequencies below 1 kHz. Significant correlations were also found between the tympanometrically determined peak total compliance and |ECR|2 and VU at frequencies below 1 kHz. The results suggest that middle ear compliance contributes significantly to the measured power reflectance and umbo velocity at frequencies below 1 kHz but not at higher frequencies. Conclusions: This study has established a database of objective measurements of middle ear function (ECR, umbo velocity, tympanometry) in a population of strictly defined normal-hearing ears. These data will promote our understanding of normal middle ear function and will serve as a control for comparison to similar measurements made in pathological ears.

Third generation bisphosphonates for treatment of sensorineural hearing loss in otosclerosis

Objective To evaluate hearing outcomes in patients treated with third generation bisphosphonates for otosclerosis-related sensorineural hearing loss (SNHL). Hypothesis Otosclerosis is a disease of abnormal bone remodeling in the otic capsule. In recent years, third generation bisphosphonates, with more powerful anti-resorptive properties and increased bone affinity, have demonstrated effectiveness in the treatment of osteoporosis and other metabolic bone diseases. We hypothesized that newer generation bisphosphonates, such as risedronate and zoledronate, would be effective in slowing the progression of SNHL in patients with otosclerosis. Study Design Retrospective review. Setting Tertiary referral center, ambulatory care. Interventions Risedronate or zoledronate administration. Main Outcome Measures Bone conduction pure tone threshold averages (PTAs) and word recognition (WR) scores were examined for each ear before and after bisphosphonate treatment. Criteria for significant change were defined as greater than 10 decibels in PTA or between 4% and 18% in WR based on binomial variance. Results All 10 patients had audiometric progression of SNHL in the pretreatment monitoring interval and 12 ears met criteria for significant progression. All 10 patients (19 ears) showed at least no significant progression of SNHL (i.e., stabilization) at an average follow-up of 13 months. Two patients (3 ears) showed improvement by defined audiometric criteria. There were no major complications. Conclusion Treatment with zoledronate or risedronate stabilized progressive SNHL related to otosclerosis in this small group of patients. Further evaluation of third-generation bisphosphonate treatments is warranted.

Comparison of umbo velocity in air- and bone-conduction.

This study investigates the ossicular motion produced by bone-conducted (BC) sound in live human ears. Laser Doppler vibrometry was used to measure air conduction (AC)- and BC-induced umbo velocity (V(U)) in both ears of 10 subjects, 20 ears total. Sound pressure in the ear canal (P(EC)) was measured simultaneously. For air conduction, V(U) at standard hearing threshold level was calculated. For BC, ΔV was defined as the difference between V(U) and the tympanic ring velocity (an estimate of the skull velocity measured in the ear canal). ΔV and P(EC) at BC standard hearing threshold were calculated. ΔV at standard BC threshold was significantly smaller than V(U) at standard AC threshold between 500 Hz and 2000 Hz. Ear canal pressure at BC threshold tended to be smaller than for AC below 3000 Hz (with significant differences at 1000 Hz and 2000 Hz). Our results are most consistent with inertia of the ossicles and cochlear fluid driving BC hearing below 500 Hz, but with other mechanisms playing a significant role at higher frequencies. Sound radiated into the external ear canal might contribute to BC hearing at 3000 Hz and above.

Medical Record Documentation of Patients’ Hearing Loss by Physicians

BACKGROUNDAnecdotal evidence suggests that hearing loss, even when sufficient to prevent full access to spoken communication, often is underreported by patients and not documented by physicians. No published studies have investigated this issue quantitatively.OBJECTIVETo assess the documentation of hearing loss in comprehensive physician notes in cases where the patients are known to have substantial binaural loss.DESIGNElectronic medical record (EMR) notes for 100 consecutive patients with substantial binaural hearing loss were reviewed retrospectively at a large academic medical center. All records reviewed were created within 2 years before the patient’s audiometry. Comprehensive physician notes containing the headings “History” and “Physical Exam” were examined for documentation of hearing loss and scored as: no mention of loss; finding of loss; or hearing reported as normal.PARTICIPANTSConsecutive adult patients with substantial binaural hearing loss by audiometry who also had a comprehensive medical assessment in their electronic medical record created within 2xa0years before audiometry.RESULTSThirty-six percent of EMRs had no mention of hearing loss, 28% reported some loss, and 36% percent indicated that hearing was normal.CONCLUSIONSSubstantial hearing loss, sufficient to prevent effective communication in the medical setting, often is underdocumented in medical records.

Spectrum of Third Window Abnormalities: Semicircular Canal Dehiscence and Beyond

SUMMARY: Third window abnormalities are defects in the integrity of the bony structure of the inner ear, classically producing sound-/pressure-induced vertigo (Tullio and Hennebert signs) and/or a low-frequency air-bone gap by audiometry. Specific anatomic defects include semicircular canal dehiscence, perilabyrinthine fistula, enlarged vestibular aqueduct, dehiscence of the scala vestibuli side of the cochlea, X-linked stapes gusher, and bone dyscrasias. We discuss these various entities and provide key examples from our institutional teaching file with a discussion of symptomatology, temporal bone CT, audiometry, and vestibular-evoked myogenic potentials.

Long-term Incidence and Degree of Sensorineural Hearing Loss in Otosclerosis

Objectives: 1) To evaluate the long-term incidence and degree of the sensorineural component of hearing loss (SNHL) in patients with otosclerosis after accounting for expected age-related hearing loss. 2) To identify variables that might predict development of sensorineural hearing loss due to otosclerosis. Study Design: Retrospective audiometric database and chart review. Setting: Tertiary referral center. Patients: Consecutive patients with otosclerosis observed between 1994 and 2004, with ≥10 years follow-up, excluding patients with postoperative hearing loss or surgery before the initial audiogram. Intervention: Bone conduction (BC) thresholds at 0.5, 1, 2, and 4u200akHz and Word Recognition. Main Outcome Measure: BC threshold change (BCTC) over ≥10 years minus estimated age-related threshold change (ARTC) specific to age and sex for each patient (based on ISO 7029 reference population). Results: Three-hundred fifty-seven ears (290 patients) met study criteria, including 217 ears that had undergone stapedectomy during the study period. Mean follow-up was 14.0 years. The average BCTC after subtracting estimated ARTC was 4.6, 2.6, 3, and 2.7 dB for 0.5, 1, 2, and 4 kHz frequencies, respectively. However, 34% of ears (122 ears) had clinically significant progression of SNHL during the study period (>10 dB BCTC beyond expected ARTC at ≥2 frequencies). Multivariate analysis demonstrated that the probability of developing clinically significant SNHL was higher for women (odds ratio 1.86, pu200a=u200a0.018) and lower for operated patients (odds ratio 0.46, pu200a=u200a0.002). Conclusion: The average long-term sensorineural hearing loss due to otosclerosis was statistically significantly more than for age alone at each frequency, but these average values (from 2.6 to 4.6u200adB for tested frequencies) were clinically insignificant. Approximately one-third of patients with otosclerosis demonstrated a clinically significant progression of the sensorineural component of hearing loss, with the average BCTC above expected age-related changes ranging from 10.2 to 14.6u200adB for tested frequencies among this subgroup.