Association of cervical vestibular-evoked myogenic potential tuning property test results with MRI findings of endolymphatic hydrops in Meniere's disease.

PURPOSE: To examine the concordance between cervical vestibular-evoked myogenic potential (cVEMP) tuning property test results and MRI findings of endolymphatic hydrops (EH). METHODS: Fourteen subjects (age 24-76 years) that had been diagnosed with unilateral definite Meniere's disease (MD) (N = 8) or unilateral probable MD (N = 6) were enrolled. All of the subjects underwent cVEMP tests (using 500 Hz and 1000 Hz tone bursts), pure-tone audiometry, and gadolinium-enhanced 3 T-MRI. To examine tuning properties of cVEMP, the 500-1000 Hz amplitude ratio was calculated as the SLOPE. The results of the cVEMP tuning property test results were compared with EH-related MRI findings. RESULTS: EH positivity in both the cochlea and vestibule on MRI was observed in 7 of the 8 affected ears of definite MD and 3 of the 6 affected ears of probable MD, although it was only in one of the 14 unaffected ears. EH(+) or no response (NR) in cVEMP tuning property test was significantly associated with EH positivity on MRI, while EH(-) in the cVEMP tuning property test was significantly associated with EH-negativity on MRI (p = 0.0016 Fisher's exact test test). CONCLUSION: EH(+) or NR in the cVEMP tuning property test correspond well to EH positivity in the MRI findings. The cVEMP tuning property test is useful for screening and following up EH.

Effects of nasal septum perforation repair surgery on three-dimensional airflow: an evaluation using computational fluid dynamics.

The purpose of this research is to determine the cause of nasal perforation symptoms and to predict post-operative function after nasal perforation repair surgery. A realistic three-dimensional (3D) model of the nose with a septal perforation was reconstructed using a computed tomography (CT) scan from a patient with nasal septal defect. The numerical simulation was carried out using ANSYS CFX V13.0. Pre- and post-operative models were compared by their velocity, pressure gradient (PG), wall shear (WS), shear strain rate (SSR) and turbulence kinetic energy in three plains. In the post-operative state, the crossflows had disappeared, and stream lines bound to the olfactory cleft area had appeared. After surgery, almost all of high-shear stress areas were disappeared comparing pre-operative model. In conclusion, the effects of surgery to correct nasal septal perforation were evaluated using a three-dimensional airflow evaluation. Following the surgery, crossflows disappeared, and WS, PG and SSR rate were decreased. A high WS.PG and SSR were suspected as causes of nasal perforation symptoms.

Habituation disorders in auditory middle latency response of persistent postural-perceptual dizziness patients.

Objectives: To study habituation disorders in auditory middle latency response (AMLR) to repetitive stimuli of persistent postural-perceptual dizziness (PPPD) patients. Subjects: Twenty-eight PPPD (10 men and 18 women, mean 59.5 years of age, 26-81 years of age) were enrolled. For comparison, data of 13 definite vestibular migraine (VM) patients (3 men, 10 women, mean age 45.5), 13 definite unilateral Meniere's disease (MD) patients (2 men, 11 women, mean age 50.6), and 8 healthy control (HC) subjects (2 men, 6 women, mean age 37.1) in the previous study were utilized. Methods: The electrodes were placed on the vertex and the spinal process of the fifth cervical vertebra. Clicks (0.1 msec, 70 dB nHL) were binaurally presented and averaged (800 times). Averaged responses were divided into 4 sets (S1 to S4) according to the temporal order. As peaks, Na, and Pa were identified, and relative Na-Pa amplitudes in S2-S4 to S1 were analyzed. Results: The mean relative amplitude of PPPD patients showed lack of habituation (potentiation) as shown in VM patients, although the extent of potentiation was weaker than VM. Comparison of relative S4 amplitudes showed significant differences among the 4 groups (p = 0.0013 one-way ANOVA), Multiple comparison revealed significant differences between PPPD and MD (p = 0.0337 Dunnet's test). Conclusion: PPPD patients showed lack of habituation (potentiation) of Na-Pa amplitude in AMLR to repetitive stimuli. Lack of habituation (potentiation) might be associated with sensory processing disorders in PPPD.

Developmental changes in the responsiveness of rat spiral ganglion neurons to neurotrophic factors in dissociated culture: differential responses for survival, neuritogenesis and neuronal morphology.

The way that the development of the inner ear innervation is regulated by various neurotrophic factors and/or their combinations at different postnatal developmental stages remains largely unclear. Moreover, survival and neuritogenesis in deafferented adult neurons is important for cochlear implant function. To address these issues, developmental changes in the responsiveness of postnatal rat spiral ganglion neurons (SGNs) to neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were examined by using a dissociated cell culture system. SGNs at postnatal day (P) 0, P5 and P20 (young adult) were cultured with the addition of NT-3, BDNF, or LIF or of a combination of NT-3 and BDNF (N + B) or of NT-3, BDNF and LIF (ALL factors). SGNs were analyzed for three parameters: survival, longest neurite length (LNL) and neuronal morphology. At P0, SGNs required exposure to N + B or ALL factors for enhanced survival and the ALL factors combination showed a synergistic effect much greater than the sum of the individual factors. At P5, SGNs responded to a wider range of treatment conditions for enhanced survival and combinations showed only an additive improvement over individual factors. The survival percentage of untreated SGNs was highest at P20 but combinations of neurotrophic factors were no more effective than individual factors. LNL of each SGN was enhanced by LIF alone or ALL factors at P0 and P5 but was suppressed by NT-3, BDNF and N + B at P5 in a dose-dependent manner. The LNL at P20 was enhanced by ALL factors and suppressed by N + B. Treatment with ALL factors increased the proportion of SGNs that had two or more primary neurites in all age groups. These findings suggest that NT-3, BDNF, LIF and their combinations predominantly support different ontogenetic events at different developmental stages in the innervation of the inner ear.

Effect of vestibular dysfunction on the development of gross motor function in children with profound hearing loss.

OBJECTIVE: To evaluate the function of the superior and inferior vestibular nerve systems in children with profound sensorineural hearing loss, and to assess the influence of dysfunction of each vestibular nerve system on the development of gross motor function. STUDY DESIGN: Retrospective study. SETTING: A tertiary referral center. METHODS: Eighty-nine children (age range: 20-97 months) with profound sensorineural hearing loss who were due to undergo cochlear implant surgery were recruited. Function of the superior vestibular nerve system was evaluated by the damped rotation test and the caloric test, whereas functions of the inferior vestibular nerve systems were evaluated by the vestibular evoked myogenic potential (VEMP) test. Gross motor development was assessed using the age of acquisition of head control and independent walking. RESULTS: Among the children able to complete the vestibular function tests, abnormalities were found in 20% (16 of 84 children) in the damped rotation test, 41% (31 of 75 children) in the caloric test and 42% (26 of 62 children) in the VEMP test. Children who showed abnormal responses in the vestibular function tests showed significantly delayed acquisition of head control (p < 0.05) and independent walking (p < 0.05) in comparison with children with normal responses. The children who showed abnormal responses in all 3 vestibular tests showed the greatest delay in acquisition of gross motor function in comparison with the other groups. CONCLUSIONS: Children with profound hearing loss tend to have dysfunction in the superior as well as the inferior vestibular nerve systems. Both the superior and inferior vestibular nerve systems are important for the development of gross motor function in children.

Evaluation of the internal structure of normal and pathological Guinea pig cochleae using optical coherence tomography.

Optical coherence tomography (OCT) makes it possible to visualize the internal structures of several organs, such as the eye, in vivo. Although visualization of the internal structures of the inner ear has been used to try and identify certain pathological conditions, attempts have failed mainly due to the thick bony capsule surrounding this end organ. After decalcifying the bony wall of the cochlea with ethylenediamine tetraacetic acid, we could clearly visualize its internal structures by using OCT. We identified endolymphatic hydrops, strial atrophy and damage to the organ of Corti, evident as a distention of Reissner's membrane, thinning of the lateral wall and flattening of the organ of Corti, respectively. When specimens embedded in paraffin, sliced and stained with hematoxylin and eosin (HE) were examined under a light microscope, the OCT images of normal and pathological cochleae were virtually identical with those of the HE specimens, except that the HE specimens exhibited several artifacts unrecognized in OCT images, which were considered to be induced during the preparation process. Since OCT enables one to obtain arbitrary plane images by manipulating the slice axis of the specimens and avoids any misinterpretation due to artifacts induced during histological preparation, our technique would be useful for examining cochlear pathologies without or prior to histological evaluations.

Diagnostic usefulness of multifrequency tympanometry for Ménière's disease.

Multifrequency tympanometry (MFT) is the measurement of the impedance of the middle ear transmission system at a wide range of frequencies from 200 Hz to 2 kHz. A potential use of MFT as a new diagnostic tool for detecting endolymphatic hydrops has recently been reported. However, its clinical usefulness for diagnosing Ménière's disease (MD) remains unclear. To evaluate the clinical usefulness of MFT as a new qualitative and diagnostic test for MD, we performed MFT in 70 patients with unilateral or bilateral MD and in 29 normal control subjects. The width of double peaks in the admittance tympanograms (Y width) at 2 kHz and the resonance frequency (RF) were analyzed, and receiver operating characteristic (ROC) curves were constructed. The Y width in MD-affected ears was significantly greater than that in control ears (p < 0.001). The RF in MD-affected ears was significantly lower than that in control ears (p < 0.01). Neither the Y width nor RF had a significant relationship with hearing levels or the results of caloric and vestibular myogenic potential testings. The area under the ROC curve was 0.71 for the Y width and 0.66 for the RF. At the optimal cutoff points, the sensitivity and specificity of the Y width were 47.3 and 86.8%, respectively, and those of the RF were 41.3 and 84.2%, respectively. These results indicated that MFT is significantly associated with the presence of MD, but its diagnostic accuracy is only modest. MFT is a simple, noninvasive test, which should be considered as a complementary test in the diagnosis of MD.

Isolated bilateral posterior semicircular canal hypofunction: comparison with bilateral vestibulopathy.

BACKGROUND: Chronic unsteadiness is a common complaint at vestibular clinics. Bilateral vestibulopathy (BVP) is a major cause of chronic unsteadiness but is often overlooked. Although diagnostic criteria for BVP have been established by the Barany Society, isolated vertical canal hypofunction can remain undiagnosed. Recently, the video head-impulse test has enabled clinicians to assess vertical semicircular canal function at clinics. OBJECTIVE: This study aimed to compare the features of isolated bilateral posterior semicircular canal hypofunction (IBPH) with those of BVP diagnosed based on the Barany criteria. METHODS: The clinical data of 8 IBPH patients that had been diagnosed using our diagnostic criteria (sex, age, subjective symptoms, questionnaire, video head-impulse test and stabilometry) were analyzed and compared with those of 6 BVP patients diagnosed using the Barany criteria. RESULTS: The IBPH patients were all aged >70 years, while the age range of the BVP patients was wider. While the BVP patients complained of both oscillopsia during body movement and unsteadiness in darkness, the IBPH patients complained of unsteadiness in darkness without oscillopsia during body movement. The IBPH patients exhibited milder clinical findings than the BVP patients. CONCLUSION: IBPH can cause mild unsteadiness in the elderly. SIGNIFICANCE: Clinicians should be aware that IBPH can cause unsteadiness in the elderly.

Higher Cardio-Ankle Vascular Index Values in Patients With Vestibular Neuritis May Indicate a Better Prognosis.

BACKGROUND: The presumed etiology of vestibular neuritis (VN), a sudden onset of spontaneous vertigo without auditory or cranial nerve symptoms, includes viral infections and vascular disorders. However, no clinical test for estimating vascular disorders in VN has been reported. Moreover, estimating the etiology of VN is important to predict the prognosis and select appropriate treatment. This study aimed to evaluate the cardio-ankle vascular index (CAVI), which reflects arterial stiffness and elasticity, as an additional indicator for estimating the prognosis and etiology of VN. MATERIALS AND METHODS: Among 207 consecutive patients with suspected VN, 88 patients diagnosed with definite VN were enrolled. Age, initial and final percent canal paresis (CP) in the caloric test, CAVI, presence or absence of vestibular-evoked myogenic potential asymmetry, and medical history were evaluated using univariate and multivariate analyses. RESULTS: Patients with VN with high CAVI had a better prognosis than those with low CAVI. High CAVI was a factor for improvement in percent CP, in addition to younger age and less severe initial percent CP in the Cox proportional hazard model. CONCLUSION: CAVI can be an additional indicator for estimating the prognosis and etiology of VN. This indicator can potentially be applied to other diseases, including vascular disorders with other etiologies.

High Cardio-Ankle Vascular Index Values in Idiopathic Sudden Sensorineural Hearing Loss Patients Indicate Better Prognosis.

OBJECTIVE: Vascular disorders and viral infections are the presumed etiologies of idiopathic sudden sensorineural hearing loss (ISSNHL) and acute sensorineural hearing loss, with no identifiable cause. However, no clinical test for estimating the extent of vascular involvement in ISSNHL has been reported despite its potential impact on prognosis and treatment. We investigated the correlation between the cardio-ankle vascular index (CAVI), which reflects arterial stiffness and elasticity, and hearing improvement to ascertain its usefulness as an additional indicator of ISSNHL prognosis and etiology. METHODS: We enrolled 182 patients diagnosed with definite ISSNHL. The percentage of mild ISSNHL patients and that of patients experiencing no change were compared between the high-CAVI and low-CAVI groups. Age, initial and final pure-tone average (PTA) values, CAVI, presence or absence of vertigo, and medical histories were retrospectively reviewed and included in univariate and multivariate analyses. RESULTS: The percentage of mild ISSNHL patients was smaller in the high-CAVI group than in the low-CAVI group, whereas the percentage of patients experiencing no change was smaller in the high-CAVI group than in the low-CAVI group, although patients in the high-CAVI group were significantly older than those in the low-CAVI group. The Cox proportional hazard model revealed that high CAVI, hypertension, younger age, and initial PTA <90 dB were associated with hearing improvement. CONCLUSIONS: ISSNHL in patients with high CAVI was more severe but had a better prognosis than that in those with low CAVI. CAVI may help evaluate diseases of vascular and other etiologies, as well as ISSNHL.

The Caloric Test Is More Consistent With the Presence of Endolymphatic Hydrops Than the Vestibular-Evoked Myogenic Potential Test in Meniere's Disease.

Objective This study aimed to investigate the correlation between enhanced inner ear magnetic resonance imaging (MRI) findings and vestibular and cochlear function test results in patients with definite Meniere's disease and confirmed endolymphatic hydrops. Methods Among 70 consecutive patients diagnosed with definite Meniere's disease, 49 underwent contrast-enhanced 3-T inner ear MRI. The patients also underwent pure-tone audiometry, glycerol, caloric, and vestibular-evoked myogenic potential (VEMP) tests. Correlations between the pure-tone audiometry, glycerol test, caloric test, VEMP test, and MRI findings were evaluated using the chi-square test or Fisher's exact test, Student's t-test, one-way ANOVA, and Bonferroni's post-hoc test. Results Contrast-enhanced inner ear MRI revealed that 33 of 49 patients (67.3%) had endolymphatic hydrops. Among them, 19 patients had bilateral endolymphatic hydrops, and 14 had unilateral hydrops. The mean hearing threshold was higher in patients with endolymphatic hydrops than those without (p< 0.001). The proportion of patients with positive glycerol test results was higher among those with endolymphatic hydrops than in those without (p= 0.01). The rate of abnormal caloric response in patients with and without endolymphatic hydrops was not significantly different (p= 0.09). Furthermore, the rate of abnormal VEMP response in patients with and without endolymphatic hydrops was not significantly different (p= 0.70). On the affected side, in the caloric test, the ratio of the presence of vestibular and cochlear hydrops was similar (p= 1.00). On the affected side, in the VEMP test, the ratio of the presence of vestibular and cochlear hydrops was also similar (p= 0.80). The consistency of the caloric test in detecting cochlear hydrops was higher than that of the VEMP test (p= 0.04). The consistency of the caloric test in detecting vestibular hydrops tended to be higher (but not significantly) than that of the VEMP test (p= 0.11). Conclusion The cochlea and vestibule on the clinically affected side were more likely to have endolymphatic hydrops revealed by contrast-enhanced 3-T inner ear MRI than on the unaffected side. The sum of the three low frequencies (125, 250, and 500 Hz) of the pure-tone audiometry was higher in patients with endolymphatic hydrops than in those without endolymphatic hydrops. The caloric test was more consistent in detecting endolymphatic hydrops, especially cochlear hydrops, than the VEMP test in patients with definite Meniere's disease. The results of this study may contribute to the future diagnosis of Meniere's disease and improve the understanding of endolymphatic hydrops.

Unidirectional rotations produce asymmetric changes in horizontal VOR gain before and after unilateral labyrinthectomy in macaques.

Unilateral vestibular lesions cause marked asymmetry in the horizontal vestibulo-ocular reflex (VOR) during rapid head rotations, with VOR gain being lower for head rotations toward the lesion than for rotations in the opposite direction. Reducing this gain asymmetry by enhancing ipsilesional responses would be an important step toward improving gaze stability following vestibular lesions. To that end, there were two goals in this study. First, we wanted to determine whether we could selectively increase VOR gain in only one rotational direction in normal monkeys by exposing them to a training session comprised of a 3-h series of rotations in only one direction (1,000°/s² acceleration to a plateau of 150°/s for 1 s) while they wore 1.7 × magnifying spectacles. Second, in monkeys with unilateral vestibular lesions, we designed a paradigm intended to reduce the gain asymmetry by rotating the monkeys toward the side of the lesion in the same way as above but without spectacles. There were three main findings (1) unidirectional rotations with magnifying spectacles result in gain asymmetry in normal monkeys, (2) gain asymmetry is reduced when animals are rotated towards the side of the labyrinthectomy via the ipsilesional rotation paradigm, and (3) repeated training causes lasting reduction in VOR gain asymmetry.

Indication of the side of delayed endolymphatic hydrops by vestibular evoked myogenic potential and caloric test.

OBJECTIVE: Delayed endolymphatic hydrops (DEH) can be clinically classified into ipsi- and contralateral types. This study aims to investigate the relationship between the results of vestibular evoked myogenic potential (VEMP) and caloric testing and the clinical type of DEH. METHODS: The data of 33 patients with DEH who underwent both VEMPs and caloric testing were retrospectively examined. The type of DEH was judged from its clinical and audiological course. Theasymmetry ratios of the VEMPs and canal paresis on the caloric test were measured. RESULTS: The results of VEMP and the caloric testing were consistent with the type of DEH in 61 and 76% of DEH patients, respectively. Combined use of VEMP and caloric testing correctly identified the type of DEH in 82% of patients. CONCLUSIONS: The combined use of VEMP and caloric testing can indicate the type of DEH at a reasonably high rate, but inconclusively.

Fusiform aneurysm of the basilar artery presenting as a cerebellopontine angle mass.

It is extremely rare that nonsaccular intracranial aneurysms are located at the cerebellopontine angle. A 60-year-old woman presented with dizziness and left-sided sensorineural hearing loss that had developed gradually for 6 months. Magnetic resonance imaging scan and magnetic resonance angiography revealed that the basilar artery was ectatic and markedly displaced to the cerebellopontine angle. The association between otoneurological findings and radiological findings is discussed.

Two cases of Tullio phenomenon in which oval and round window reinforcement surgery was effective.

AIM: To report the effect of oval and round window reinforcement surgery performed in two patients with the Tullio phenomenon. Case 1: A male with bilateral superior canal dehiscence syndrome. Downbeat nystagmus with leftward horizontal eye movement was recorded in an electronystagmogram using a pure-tone sound of 110dB at 2000 or 4000Hz in the right ear. Case 2: A female who had undergone stapes surgery. Computed tomography revealed an ossicular prosthesis in the vestibule. An audiogram indicated mild to moderate hearing impairment in the right ear. Leftward horizontal nystagmus was recorded in an electronystagmogram using a pure-tone sound of 110dB at 500 or 1000Hz in the right ear. Surgical findings indicated that the prosthesis was inserted deep into the oval window, which was closed with thin connective tissue. OUTCOMES: After oval and round window reinforcement surgery was performed in the right ear, and loud, pure-tone sounds elicited neither nystagmus nor dizziness in either patient.

Testing of vibratory thresholds as a clinical examination for patients with unsteadiness due to somatosensory disorders.

The somatosensory system is an important component for balance control. Disorders of this system are characterized by postural unsteadiness and could be assessed by vibratory sensation. However, the measurement of vibratory thresholds (VTs) has been rarely employed as a clinical test for patients with unsteadiness. This study aimed to evaluate the difference in vibratory thresholds between patients with somatosensory disorders and healthy volunteers, and to provide a means for evaluating somatosensory disorders in patients with balance problems. Using a vibrometer and a force-measuring platform, VTs and postural balance in 108 healthy volunteers (age, 17-79) and 19 patients with somatosensory disorders (age, 60-79) were examined. VTs of the plantar surface, as well as total length of the path and envelope area (ENV) of posturograms, in patients with somatosensory disorders were significantly larger than those in healthy volunteers. Regression analyses showed that VTs> or =28dB (peak-to-peak amplitude, 24 microm) of the plantar surface at 125Hz and ENV> or =10 cm(2) were significant indices for unsteadiness due to somatosensory disorders. VT testing of the plantar surface as well as posturography appears to be useful as a clinical examination for patients with unsteadiness.

Prediction of the prognosis of Bell's palsy using multivariate analyses.

OBJECTIVES: This study aimed to establish more reliable formulae for predicting the prognosis for patients with Bell's palsy at initial examination. PATIENTS: One hundred four consecutive patients with Bell's palsy whose facial movement was either completely recovered or unchanged for more than 6 months. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Multivariate analyses were performed using the following variables: Age, House-Brackmann score (H-B), electroneuronography (ENoG), nerve excitability test (NET), blink reflex, and stapedial muscle reflex on initial examination. RESULTS: Duration to maximal recovery can be predicted with the adjusted coefficient of 0.51 using H-B, ENoG, stapedial muscle reflex, and NET. Whether complete recovery would be achieved can be predicted with the Nagelkerke coefficient of determination of 0.72 using age, H-B, ENoG, and NET. CONCLUSION: This study suggested that the prognosis of patients who recovered early can be predicted more precisely; however, the prognosis of patients who recovered late and incomplete could not be predicted easily.

Wall-eyed bilateral internuclear ophthalmoplegia in a patient with progressive supranuclear palsy.

Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is a rare disorder consisting of a bilateral adduction deficit and primary gaze position exotropia. Associated with bilateral medial longitudinal fasciculus lesions, it has been mostly reported in patients with multiple sclerosis and brainstem stroke. A 72-year-old man with characteristic clinical features of progressive supranuclear palsy (PSP) later developed WEBINO. Brain MRI revealed atrophy of the midbrain tegmentum. Caloric irrigation revealed intact horizontal eye movements in both eyes. We believe this to be the first report of WEBINO in PSP. The preservation of vestibulo-ocular horizontal eye movements supports the notion that the WEBINO in this condition was caused by a supranuclear rather than a nuclear lesion and suggests the possibility that even in other causes of WEBINO, the lesion is supranuclear and not in the medial rectus subnucleus as is often suggested.

Abnormal deviation of subjective visual horizontal in patients with vestibular schwannoma.

OBJECTIVES: This study was aimed to examine the correlation between the results of subjective visual horizontal (SVH) and other vestibular function tests in patients with untreated unilateral vestibular schwannoma (VS). METHODS: The subjects comprised 40 consecutive patients (17 men, 23 women) with VS who underwent vestibular function tests before surgery and had surgically and histopathologically confirmed unilateral VS. The vestibular function tests included SVH, caloric, and vestibular evoked myogenic potential (VEMP) tests. RESULTS: Of the 40 patients, 31 (77.5%) showed deviation of the SVH toward the affected side down. Especially in 8 patients (20.0%), abnormal deviation (more than 2.2 degrees) toward the affected side down was seen. None of the patients showed abnormal deviation toward the unaffected side down. On the caloric test, the proportion of absent caloric responses and the percent canal paresis in patients with an abnormal SVH was significantly higher than those in patients with a normal SVH. The proportion of abnormal VEMP responses was higher and the percent VEMP asymmetry was smaller in patients with an abnormal SVH than in patients with a normal SVH; however, the differences were not significant. CONCLUSIONS: Abnormal results on the caloric test and/or VEMP test were more frequently seen in VS patients with abnormal deviation of the SVH.

Time course of apoptotic cell death in guinea pig cochlea following intratympanic gentamicin application.

CONCLUSIONS: The present study showed that the molecular signal that promotes the death of cochlear hair cells (HCs) induced by intratympanic gentamicin application is significant before the manifestation of morphological and functional changes. OBJECTIVES: The effect of agents that protect the HCs from aminoglycoside ototoxicity is influenced by the timing of their administration. However, morphological, functional and molecular changes in the cochlea in the early stage following aminoglycoside application have rarely been studied. Therefore, we examined the chronological changes in the cochlea following intratympanic gentamicin application. MATERIALS AND METHODS: Small pieces of gelatin sponge soaked with gentamicin (40 mg/ml) were placed on the round window membrane of mature guinea pigs, and the tympanic bulla was filled with gentamicin solution. They were euthanized at 6, 12, 18, 24, and 48 h following gentamicin application. Auditory brainstem responses (ABRs) were measured before gentamicin application and immediately before euthanasia, and the extent of missing and TUNEL-positive HCs was evaluated. RESULTS: ABR thresholds significantly increased 18 h or later following gentamicin application, and the loss of HCs was seen at 24 and 48 h. While functional and morphological changes were not evident until 18 h after gentamicin application, substantial amounts of TUNEL-positive HCs appeared at 12 h.