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PubMed2003

Free radical scavenger protects against inner hair cell loss after cochlear ischemia.

We investigated the protective effects of edaravone, a free radical scavenger, against ischemic damage of inner hair cells (IHCs) in gerbils. Cochlear ischemia was induced in the animals by occluding the vertebral arteries bilaterally for 15 min. Edaravone (1 mg/kg, i.v.) or saline was administered 1 h after ischemia. Hearing was assessed by auditory brain response (ABR). In animals treated with saline, the ABR threshold shift was 24.1 dB and there was a 26.5% decrease in the number of IHCs. By contrast, in animals treated with edaravone, the threshold shift was 7.5 dB and only 8.8% of IHCs was lost. These results suggest that edaravone protects against damage to the inner ear following transient ischemia.

Analysis of Variance↗
PubMed2005

Combined oral delivery of ebselen and allopurinol reduces multiple cisplatin toxicities in rat breast and ovarian cancer models while enhancing anti-tumor activity.

The chemoprotective effects of combined ebselen and allopurinol in breast (MTLn3) and ovarian (NuTu-19) cancer models using a repeated cisplatin dosing schedule (6 mg/kg i.p.x3 weeks) were studied. Otoprotection was evaluated using auditory evoked brainstem response (ABR) to determine threshold and latency shifts, and outer hair cell counts. Nephroprotection was analyzed by serological markers [blood urea nitrogen (BUN) and creatinine] and histological evaluation. Myelotoxicity was quantified using cytological counts for platelets and changes in hematocrit. Hepatotoxicity was determined by changes in the serological markers amino alanine transferase (ALT) and aspartate amino transferase. Significant chemoprotective effects were observed for multiple organ systems including oto- (ABR threshold shifts for click and 24-kHz stimuli, p<0.05, 8 and 16 kHz, p<0.01, MTLn3 group; hair cell counts, p<0.05 both groups), nephro- (BUN and creatinine, p<0.01), myelo- (platelet p<0.05, hematocrit p<0.05) and hepatotoxicity (ALT p<0.05) in rats receiving oral ebselen and allopurinol. Importantly, the anti-tumor activity of cisplatin was not compromised. On the contrary, improved mortality, morbidity and outcome were observed in the ovarian cancer model. This combined oral formulation of ebselen and allopurinol is an attractive candidate for clinical evaluation.

Administration, Oral↗
PubMed2000

Magnetic resonance imaging for evaluation of otic labyrinth pathology.

The auditory (cochlear) labyrinth, the cochlea, holds the hearing sensory receptors. The vestibular labyrinth contains the sensory receptors for balance, which lie in the three semicircular canals and in the otolithic organs (the saccule and utricle). Pure tone audiometry and brain stem evoked audiometry can help to differentiate a peripheral cochlear disorder from central lesion. The type of nystagmus, severity of postural instability, and neurological evaluation can help to differentiate a peripheral vestibular disorder from a central vestibular lesion. The decision whether to perform an appropriate imaging such as brain imaging versus labyrinthine imaging depends on the clinical and paraclinical information provided to the radiologist by the neurotologist, neurologist, or other clinicians. The magnetic resonance imaging characteristics of peripheral cochlear and vestibular lesions are the main focus of this article.

Cochlear Diseases↗
PubMed2003

Right-to-left shunt and risk of decompression illness with cochleovestibular and cerebral symptoms in divers: case control study in 101 consecutive dive accidents.

OBJECTIVE: We investigated the role of right-to-left shunt with standardized transcranial Doppler ultrasonography in a large population of divers referred for symptoms of decompression illness. DESIGN: Case series compared with a control group. SETTING: Military teaching hospital, hyperbaric unit. PATIENTS: Patients were 101 consecutive divers with clinical evidence of decompression illness and a control group of 101 healthy divers. INTERVENTION: Specification of the type of decompression illness involved and detection/evaluation of right-to-left shunt by standardized transcranial Doppler. The degree of right-to-left shunt was defined as major if the number of high-intensity transient signals in the middle cerebral artery was >20. MEASUREMENTS AND MAIN RESULTS: We evaluated the odds ratios by logistic regression analysis with vs. without right-to-left shunt for subjects with cochleovestibular symptoms, cerebral decompression illness, spinal decompression illness, and Caisson sickness. Of the 101 divers presenting with decompression illness, transcranial Doppler detected a right-to-left shunt in 59 (58.4%), whereas control subjects demonstrated a right-to-left shunt in 25 cases (24.8%; odds ratio, 4.3; 95% confidence interval, 2.3-7.8; p=.09). When a right-to-left shunt was detected, the right-to-left shunt was major in 12 of 25 patients in the control group and in 49 of 59 patients in the decompression illness group (odds ratio, 8.7; 95% confidence interval, 4.2-18.0; p<.001). Within the decompression illness group, the proportion of major right-to-left shunt was 24 of 34 (odds ratio, 29.7; 95% confidence interval, 10.0-87.2; p<.0001) in the cochleovestibular subgroup, 13 of 21 (odds ratio, 24.1, 95% confidence interval, 6.8-86.0, p< 0.0001) in the cerebral decompression illness subgroup, ten of 31 (odds ratio, 3.9; 95% confidence interval, 1.5-10.3; p<.01) in the spinal decompression illness subgroup, and two of two (odds ratio, 1.1; 95% confidence interval, 0.2-5.7; p=.9) in the subgroup of divers with Caisson sickness. CONCLUSION: Based on our results, we conclude that major right-to-left shunt was associated with an increased incidence of cochleovestibular and cerebral decompression illness, suggesting paradoxical embolism as a potential mechanism.

Adult↗
PubMed1992

Interaction of click intensity and cochlear hearing loss on auditory brain stem response wave V latency.

Auditory brain stem responses (ABRs) to 95, 80, 60, 40, and 30 dB nHL clicks were retrospectively studied from 103 patients (194 ears) with various degrees of cochlear impairment. Hearing loss and sample size were balanced across gender. Results indicate that the slope of the wave V latency versus 4000 Hz hearing loss function doubles as click intensity is decreased from 80 (0.01 msec/dB HL) to 60 nHL (0.02 msec/dB HL). Overall results indicate a slope increase of 0.0004 msec for each decibel decrease in click intensity from 95 to 30 dB nHL. Intersubject variability increased with increased hearing loss and/or decreased stimulus intensity. The effects of hearing loss on wave V latency are minimal, and intersubject variability is less if high-intensity clicks (greater than or equal to 95 dB nHL) are used. No differences in the effects of hearing loss on wave V latency were seen between males and females. Latency corrections for cochlear hearing loss should, therefore, consider stimulus intensity.

Acoustic Stimulation↗
PubMed1998

An animal model of auditory neuropathy.

OBJECTIVE: We describe an animal model of auditory neuropathy in which subjects have extensive, scattered inner haircell loss but with a relatively intact outer haircell population. DESIGN: Such a pattern of cochlear haircell damage can be produced in the chinchilla by treatment with the anticancer agent carboplatin. RESULTS: In these subjects, otoacoustic emissions (OAEs) and cochlear microphonics remain normal while auditory brain stem evoked potential (ABR) thresholds are significantly elevated. However, in the same subjects, central auditory neurons (in the inferior colliculus) have response thresholds that are considerably lower (by up to 50 dB) than ABR thresholds. These findings parallel the characteristics of auditory neuropathy in humans, in which absent or abnormal ABRs are recorded in patients with only mild to moderate audiometric thresholds and preserved OAEs. CONCLUSIONS: We suggest that scattered inner haircell lesions also can result from long-term cochlear hypoxia, and we propose that this is a likely candidate for the etiology of many types of auditory neuropathy in human subjects.

Animals↗
PubMed1996

Late sequelae of cochlear infection.

Inflammatory reactions within the inner ear are deleterious to cochlear function and can result in server hearing loss that does not recover. This study investigated a guinea pig model of long-term cytomegalovirus infection. At high doses active inflammation was still present after 35 days. At lower doses some ears showed partial resolution while others were still inflamed. Hearing was totally lost in all cases of persistent inflammation. There was some residual hearing in the cases that had resolved. Cochlear structures including the organ of Corti, stria vascularis, and spiral ganglion were partially degenerated. Fibrotic matrix within scala tympani was ossified in many cases. These changes are consistent with those described for human cochleas following putative viral infections.

Animals↗
PubMed1996

Association of mitochondrial DNA deletions and cochlear pathology: a molecular biologic tool.

The purpose of these experiments was to develop a method of isolation, amplification, and identification of cochlear mitochondrial DNA (mtDNA) from minute quantities of tissue. Additionally, studies were designed to detect mtDNA deletions (mtDNA del) from the cochlea that previously have been amplified from other organ systems and tissues. MtDNA del have been associated with many pathologies, including neurological disorders, sensorineural hearing loss, ischemia, cardiomyopathies, and aging. DNA was extracted from rat and human tissues, and polymerase chain reaction was used to amplify mtDNA sequences. A 360 base pair (bp) cytochrome-b gene product and the highly conserved ND1-16S ribosomal ribonucleic acid regions found only in mtDNA were amplified from all tissues. Preliminary studies have identified a 4834 bp mtDNA del in aged rats and a corresponding 4977 bp mtDNA del in aged humans. Additionally, preliminary results in human archival temporal bone studies reveal the presence of the 4977-bp mtDNA deletion in two out of three patients with presbycusis. The deletion was not evident in age-matched control patients without a history of presbycusis. This technique of mtDNA identification makes it possible to investigate specific mtDNA defects from a single cochlea, promoting the study of hereditary hearing loss and presbycusis at a molecular biologic level.

Aged↗
PubMed1997

Interaction between hypertension and diabetes mellitus in the pathogenesis of sensorineural hearing loss.

The purpose of this study is to support the hypothesis that diabetic end-organ damage of the cochlea is augmented in the setting of hypertension. A historical perspective reviewing the effects of diabetes and hypertension as causative factors in the development of sensorineural hearing loss, as well as the basic epidemiology and pathophysiology of the renal and vascular effects of diabetes and hypertension, is presented. The results of audiologic findings in insulin-dependent diabetic patients, both normotensive and hypertensive, were analyzed and correlated with the results of animal studies to support the hypothesis that sensorineural hearing loss in patients and cochlear hair cell loss in animal studies result from the effects of hypertension in conjunction with insulin-dependent diabetes mellitus.

Adult↗
PubMed1999

Relationship between cochleovestibular disorders in hemifacial spasm and neurovascular compression.

OBJECTIVE: To investigate the evolution of cochleovestibular symptoms before, during, and after microvascular decompression (MVD) of the facial nerve in hemifacial spasm. STUDY DESIGN: Prospective study in patients with hemifacial spasm. Among our 13 patients who underwent MVD of the facial nerve from 1995 to 1997, 6 had associated cochleovestibular disorders confirmed by neurotologic tests. RESULTS: In four of these patients, a concomitant compression of the eighth and facial nerves was found at surgery. Preoperative magnetic resonance angiography studies had shown three cases of this double neurovascular compression. Intraoperative auditory brainstem response monitoring showed that interposition of Teflon between vessel and facial nerve was highly critical to the auditory function. Auditory brainstem response monitoring was used to guide the surgeon during this critical phase. Surgery improved at least one cochleovestibular symptom in each patient. CONCLUSIONS: The authors propose two pathophysiologic hypotheses. First, the concomitant facial and cochleo-vestibular symptoms may be due to a hyperactivity of both the facial and vestibular nuclei. According to theories about cryptogenic hemifacial spasm, the origin of this hyperactivity could be an ectopic excitation focus. However, the two nerves may have different sites of ectopic excitation. According to the second hypothesis, a pulsatile compression of the facial nerve may be transmitted to the eighth nerve. This could take place even if only the facial nerve is in contact with a vascular loop.

Aged↗
PubMed2000

Dynamic asymmetry of the vestibulo-ocular reflex in unilateral peripheral vestibular and cochleovestibular loss.

OBJECTIVE: Rotatory tests in the horizontal plane have shown various degrees of vestibulo-ocular reflex (VOR) asymmetry in patients after surgical deafferentation of one labyrinth. The purpose of this work was to characterize dynamic horizontal VOR responses among patients presenting with a unilateral peripheral labyrinthine deficit of nonsurgical origin and to compare results in isolated vestibular loss versus cochleovestibular loss. STUDY DESIGN: This study included 40 patients who presented with an acute, spontaneous unilateral peripheral labyrinthine lesion. Twenty-two patients had vestibular loss alone (without associated hearing impairment) and 18 presented with a cochleovestibular deficit (sudden hearing loss with vertigo). The majority of these patients were part of a long-term protocol to evaluate vestibular compensation. METHODS: All patients underwent both the clockwise test and the counterclockwise rotatory test in the horizontal plane, using brief impulses of moderate intensity. Results were analyzed by a simplified model of vestibular function, allowing a parametric estimation of the response. RESULTS: A weak and transitory horizontal VOR asymmetry was observed in the 22 patients with vestibular loss. However, the 18 patients with cochleovestibular loss demonstrated a more severe and persistent asymmetry. CONCLUSIONS: This study revealed a difference in the dynamic characteristics of the horizontal VOR between patients with vestibular loss and those with cochleovestibular loss. Our results support the presence of an extensive labyrinthine lesion in cochleovestibular deficit that involves the otolith organs. The implications of this involvement on the central mechanisms of otolith-canal interaction are discussed.

Adult↗
PubMed2001

Sound-evoked myogenic potentials and responses with 3-ms latency in auditory brainstem response.

OBJECTIVES: The vestibular-evoked myogenic potential (VEMP) has shed new light on vestibular testing. A large negative deflection with a 3-ms latency within the auditory brainstem response (ABR) has been reported in some patients with deafness. This negative deflection has been termed the N3 potential and it is assumed to be a vestibular-evoked potential. This study investigated the relationship between the VEMP and the N3 potential. STUDY DESIGN: Prospective evaluation of the VEMP and the N3 potential in 21 patients. METHODS: The oto-neurological tests, including caloric test, hearing sensitivity test, VEMP, and ABR, were performed and data were analyzed. RESULTS: The average hearing threshold ranged from 65 to above 110 dB, which includes 9 (37.5%) totally deaf ears. The N3 potentials were recorded in 10 (41.7%) ears. A normal VEMP was detected in 16 (66.7%) ears. Canal paresis was observed in 11 (45.8%) ears. CONCLUSIONS: Both the VEMP and the N3 potential appear to originate from the sacculus, but because the characteristics of these two responses are not identical, additional factors might be involved in the generation of the N3 potential.

Acoustic Stimulation↗
PubMed2004

Questioning the relationship between cochlear otosclerosis and sensorineural hearing loss: a quantitative evaluation of cochlear structures in cases of otosclerosis and review of the literature.

BACKGROUND: The literature provides conflicting information regarding the prevalence and cause of sensorineural hearing loss (HL) in individuals with otosclerosis. OBJECTIVE: The purpose of this study was to further evaluate the association between involvement of the cochlear endosteal layer with otosclerosis and sensorineural HL. STUDY DESIGN: Retrospective case review. METHODS: Temporal bones and audiograms from five individuals with otosclerosis were evaluated. The cochlear elements were quantified. The location and extent of the cochlear element loss was correlated with the location and extent of endosteal involvement with otosclerosis. RESULTS: A reduction in the population of cochlear elements was observed in most individuals; however, the reduction was not proportional to the extent of endosteal involvement with otosclerosis. The cochlear elements remained normal adjacent to some areas of endosteal involvement with otosclerosis. One individual with extensive cochlear otosclerosis had normal hearing and predominantly normal cochlear elements. CONCLUSION: This study demonstrates a variable amount of degeneration of the cochlear elements in individuals with otosclerotic involvement of the endosteum. The reduction in the population of cochlear elements was not related to the extent and location of endosteal involvement with otosclerosis. These findings suggest that factors that limit the effect of otosclerotic endosteal involvement on the cochlear elements or processes that effect the cochlear elements directly and are independent of bone involvement may be present.

Aged↗
PubMed2001

Objective method for differentiating between drug-induced vestibulotoxicity and cochleotoxicity.

HYPOTHESIS: An objective direct method is proposed to differentiate between drug-induced functional vestibulotoxicity and cochleotoxicity. BACKGROUND: Many substances are ototoxic. Although there are objective methods to directly evaluate functional cochlear toxicity (auditory nerve brainstem responses [ABR]), it is more difficult to assess direct functional ototoxicity to the various vestibular end organs. METHODS: Short-latency vestibular evoked potentials (VsEP) from different vestibular end organs and ABR, were used to assess functional impairment of the vestibular and cochlear end organs caused by daily injections of the aminoglycoside amikacin (known to be preferentially cochleotoxic) in guinea pigs. RESULTS: There was no significant change in the various VsEPs. whereas ABR thresholds were elevated, confirming the selective functional cochleotoxicity previously reported, as evaluated by other (mainly nondirect) methods. CONCLUSION: This study demonstrates the feasibility in general of using short-latency evoked potentials to evaluate functional cochleotoxicity and vestibulotoxicity of ototoxic drugs and to differentiate between them.

Amikacin↗
PubMed2001

Etanercept therapy for immune-mediated cochleovestibular disorders: preliminary results in a pilot study.

OBJECTIVE: Immune-mediated cochleovestibular disorders (IMCVDs) continue to present a management challenge to the otolaryngologist. Antirheumatic agents, commonly used for IMCVDs, are associated with variable efficacy and sometimes with serious side effects. The authors describe the preliminary result of their experience in patients with IMCVDs who have been treated with etanercept, a tumor necrosis factor alpha receptor blocker, recently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care hospital. PATIENTS: Twelve patients suspected of having IMCVD who did not respond to conventional therapies or experienced side effects of the conventional therapies. INTERVENTION: Etanercept 25 mg by subcutaneous injection twice per week. MAIN OUTCOME MEASURES: The main outcome measurement was assessment of hearing change by air conduction pure tone audiograms and/or word discrimination. When present, vertigo, tinnitus, and aural fullness were assessed as well. RESULTS: Follow-up of more than 5 months was available for all patients (range, 5-12 months). Eleven (92%) of 12 patients had improvement or stabilization of hearing and tinnitus, seven (88%) of eight patients who had vertigo and eight (89%) of nine patients who had aural fullness had resolution or significant improvement of their symptoms. The benefit persisted until the last visit (5-12 months after etanercept was begun). The condition of one patient improved dramatically at first but deteriorated after 5 months. The patient's hearing was rescued and stabilized with the addition of leflunomide to etanercept. Similarly, three other patients required a second antirheumatic agent to stabilize their hearing. There were no significant side effects from the etanercept therapy. CONCLUSIONS: Our limited data suggest that etanercept therapy is safe and may be efficacious in carefully selected patients with IMCVDs, at least on a short-term basis. These preliminary efficacy and safety results appear encouraging enough to warrant further follow-up and studies for better determination of the potential clinical utility of etanercept for IMCVDs.

Adult↗