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Changes in Chinchilla Vestibular Neuroepithelia after Intratympanic Gentamicin Treatment
Research Posters
ulations using the CCI system in each cochlea were performed. To the final presentation six episodes were included in which CBF-ECochG monitoring was not obscured by background noises. Results: In the tested cochleae, always just after the first CCI system stimulation overshoot of the compound action potential (CAP) and cochlear microphonics (CM) amplitudes were observed reaching from 140% to 180% of baseline (BL). Then, systemic reduction of both CAP and CM amplitudes for all test frequencies were observed. After 30 min CM amplitudes were reduced deeper than CAP amplitudes. The second CCI stimulation evoked in all cochleae regular and fast reduction of ECochG finally reaching total reduction of CM and near-total reduction of CAP during 20-30 min. More sensitive and faster damage was shown at higher test frequencies. During all monitored episodes, CBF fluctuated slightly, however, no consistent cochlear blood flow deficit was observed. Conclusion: Even a relatively low intensity of CCI affected cochlear activity in these subjects, mostly in the high frequency basal region. Both receptor (ECochG) and neural activity (CAP) were found to be sensitive to this electrical stimulation. Significance: This experimental model of electrically induced reduction of CM and CAP amplitudes explains mechanisms of cochlear damage following CCI overstimulation R521 The Expression and Genetic Variations of Heat Shock Protein 70 in Me ´ nie ` re’s Disease Ken Hayashi, MD PhD (presenter); Ryo Kobayashi, MD; Koichi Kitamura, MD; Atsushi Shinkawa, MD Kanagawa Japan; Tokyo Japan; Tokyo Japan; Kanagawa Japan
Problem: The objectives of this study were to consider whether psychological stresses were associated with the expression and genetic variations of Heat Shock Protein 70 (HSP70) in Meniere’s disease. Methods: Fifty consecutive patients with Meniere’s disease and twenty healthy donors as control ware enrolled in this study. Single Nucleotide Polymorphism (SNP) analysis was performed making use of Masscode_ system (Shimadzu Biotech) after DNA of these blood samples was extracted using a DNA extraction kit (PAX gene DNA blood kit, Qiagen). The expression of HSP70 and HSF1 in mRNA levels was examined with RT-PCR after tRNA was extracted using a RNA extraction kit (PAX gene RNA blood kit, Qiagen). Profile of mood states (POMS) was used in order to measure the level of psychological stress. Results: The genotypes of the polymorphism HSPA1L110 and 190 were confirmed in Meniere’s disease. The HSPA1L genotype G/C was associated with psychological stress and the number of attach of Meniere’s disease. The expression of HSP70 was induced by a wide variety stresses
including psychological stress, arteriosclerosis and inflammation. On the contrary, the expression of HSP70 was reduced by depression, ageing and diabetes. The HSPA1L genotype G/C induced the expression of HSP70 at mRNA levels. POMS show that an attack of Meniere’s disease was related to stress. Conclusion: These results suggest that genetic variations of HSP70 gene and a wide variety of stresses including psychological stress may contribute to an attack of Meniere’s disease. Significance: Our data indicated the importance of HSPA1L genotype G/C and psychological stress in Meniere’s disease.
R522 Changes in Chinchilla Vestibular Neuroepithelia after Intratympanic Gentamicin Treatment Lee Ching Wu Anderson, MD (presenter); Timo P Hirvonen, MD; Mohamed Lehar, MD; Casey C. Vogelheim; John P Carey, MD Baltimore MD; Helsinki Finland; Baltimore MD; Marquette MI; Baltimore MD
Problem: Single-dose intratympanic gentamicin is used to alleviate vertigo in patients with Me´nie`re’s disease. While known as “chemical labyrinthectomy,” intratympanic gentamicin does not stop spontaneous vestibular afferent firing, although sensitivity to vestibular stimuli is markedly reduced (Hirvonen et. al., 2002). The purpose of this study was to investigate the specific qualitative and quantitative effects of single-dose intratympanic gentamicin on vestibular neuroepithelia. Methods: Adult chinchillas received a single, unilateral intratympanic gentamicin injection (26.7 mg/ml, 30 min exposure); the contralateral ears served as controls. Animals were sacrificed and fixed either 14-28 days (early) or 3 months (late) post-treatment. Semicircular canal cristae and utricular maculae were sectioned for light and electron microscopy. Results: Median vestibular hair cell nuclei per transverse section was reduced by 53% in treated cristae (p⫽0.004) and 43% in treated utricular maculae (p⫽0.04), with loss of nearly all type I hair cells. Neuroepithelial height was reduced by 21% (p⫽0.004). Median vestibular afferent bouton number was unchanged (p⫽0.2). Median vestibular efferent ending number in the late group was reduced by 48% (p⫽0.04). Median ribbon synapse number was reduced by 48% (p⫽0.008). Of the hair cells remaining after intratympanic gentamicin treatment, there was a 66% decrease in the proportion of hair cells bearing stereociliary bundles (p⬍0.001). Conclusion: A single intratympanic gentamicin treatment does not create a complete labyrinthectomy. Rather, some hair cells and their synaptic specializations are preserved, which may provide the synaptic input to maintain spontaneous firing of vestibular nerve afferents. Significance: Preservation of spontaneous firing after intratympanic gentamicin treatment may decrease the adaptive
POSTERS
P132
Otolaryngology– Head and Neck Surgery August 2005
Otolaryngology– Head and Neck Surgery Volume 133 Number 2
R523 Evaluation of Quality of Life after Intratympanic Gentamicin for Me ´ nie ` re’s Disease Animesh Samar Banerjee, MD MS FRCSI (presenter) Newcastle Upon Tyne United Kingdom
Problem: To evaluate quality of life after Intratympanic Gentamicin for Meniere’s disease Methods: This retrospective study included all patients diagnosed of Meniere’s disease according to AAO-HNS criteria (refractory to medical management), undergoing Gentamicin labyrinthectomy in this unit over the preceding three years. Other causes of hearingloss were ruled out as all patients underwent MRI scan, ENG and Sway Magnetomety. Patients underwent gentamicin infiltration at concentration of 2mls of 30mg/ml & reviewed 6 weeks later with repeat injection if no benefit. Six months after their last follow up, they were sent GBI questionnaire. Twenty one questionnaires were posted, response rate was 81%. Results: As per the responses received, total benefit of intratympanic gentamicin injection was found to be ⫹30.3. Three components of GBI were analysed separately and it was found that general benefit was maximum (⫹33.3) followed by physical benefit (⫹28.1) and social benefit (⫹21.6) Conclusion: This study suggests that gentamicin definitely improves QoL in patients with Meniere’s disease and should be the first line of treatment if medical management fails. Significance: This study suggests that gentamicin definitely improves QoL in patients with Meniere’s disease and is relatively safe in preservation of hearing. It should be the first line of treatment if medical management fails R524 Anatomy of the Approach to the Petrous Apex Through the Superior Semicircular Canal Hamid R Djalilian, MD (presenter); Gina D Jefferson, MD; Helen Xiao-ou Xu, MD Los Angeles CA; Los Angeles CA; Los Angeles CA
Problem: The goal of this study is to use high resolution CT imaging to measure the means and ranges for the surgical approach to the petrous apex through the crura of the superior semicircular canal (SCC). Methods: High-resolution CT images of the temporal bone 1.0mm apart were obtained. Identical head position was insured using fixed landmarks. All patients were 18 years of age or older. Twenty of the 116 temporal bones had pneumatiza-
tion of the petrous apex and were examined for the study. Films were read by a neurotologist and neuroradiologist for evidence of abnormalities. Measurements were made using the standard PACS (picture archiving and communication system) measurement software. Results: Seven (35%) of the 20 temporal bones had air cells between the crura of the SSC. The mean anteriorposterior (AP) dimension of the intercrural space of the SSC was 3.67⫹/-0.31mm. The mean superior-inferior dimension of the approach was 3.59⫹/-0.31mm. When air cells were present in the intercrural space, the dimensions of the approach increased to 3.93⫹/-0.61mm for the AP dimension and 3.91⫹/-0.66mm for the superior-inferior dimension. Conclusion: Our study of 20 temporal bones provides the surgeon with the mean and ranges of the dimensions of the petrous apex approach through the crura of the SSC. These measurements show that this approach is anatomically possible for drainage of petrous apex cholesterol granulomas with minimal risk to the SSC by traversing the intercrural space. Resection of petrous apex lesions is probably not possible given the small intercrural space. Significance: This study allows the clinician to understand the dimensions and plausability of the surgical approach to the petrous apex through the crura of the superior semicircular canal. R525 Capping of the Third Window: A Five-Year Review of Superior Canal Dehiscence Syndrome Nathan Wayne Hales, MD (presenter); James E Saunders, MD Oklahoma City OK; Oklahoma City OK
Problem: Superior canal dehiscence (SCD) syndrome consists of vestibular and audiologic signs and symptoms, as well as bony dehiscence over the superior semicircular canal (SSC) on temporal bone CT. Medical and surgical treatments including SSC ablation and plugging have been reported. Nevertheless, several unresolved issues remain including the constellation of symptoms considered diagnostic, the pathophysiology of certain clinical features such as self-audible eye movements, and the optimal surgical technique. Methods: A retrospective review of eight patients with signs, symptoms, and imaging findings consistent with the diagnosis of SCD are presented. These findings will be compared with previous reports of SCD. The medical and surgical management will also be presented including a technique of capping the SSC, without ablation or plugging, intended to preserve SSC function. Results: The average age was 46 years old. No prior history of related trauma or infection was identified. No familial pattern was identified. The four most common presenting symptoms were: noise and pressure-induced dizziness, roaring tinnitus, pressure sensation, and hearing loss. A significant number of patients had self-audible eye move-
POSTERS
burden for the central vestibular nuclei in patients compared to surgical labyrinthectomy. Support: Supported by NIDCD R03 DC005700, K23 DC00196-01, R01 DC02390, T32 DC00027, P30 DC05211, grants from the Finnish Medical Foundation, Finnish Academy, and American Academy of Otolaryngology-Head and Neck Surgery Foundation.
Research Posters P133
ulations using the CCI system in each cochlea were performed. To the final presentation six episodes were included in which CBF-ECochG monitoring was not obscured by background noises. Results: In the tested cochleae, always just after the first CCI system stimulation overshoot of the compound action potential (CAP) and cochlear microphonics (CM) amplitudes were observed reaching from 140% to 180% of baseline (BL). Then, systemic reduction of both CAP and CM amplitudes for all test frequencies were observed. After 30 min CM amplitudes were reduced deeper than CAP amplitudes. The second CCI stimulation evoked in all cochleae regular and fast reduction of ECochG finally reaching total reduction of CM and near-total reduction of CAP during 20-30 min. More sensitive and faster damage was shown at higher test frequencies. During all monitored episodes, CBF fluctuated slightly, however, no consistent cochlear blood flow deficit was observed. Conclusion: Even a relatively low intensity of CCI affected cochlear activity in these subjects, mostly in the high frequency basal region. Both receptor (ECochG) and neural activity (CAP) were found to be sensitive to this electrical stimulation. Significance: This experimental model of electrically induced reduction of CM and CAP amplitudes explains mechanisms of cochlear damage following CCI overstimulation R521 The Expression and Genetic Variations of Heat Shock Protein 70 in Me ´ nie ` re’s Disease Ken Hayashi, MD PhD (presenter); Ryo Kobayashi, MD; Koichi Kitamura, MD; Atsushi Shinkawa, MD Kanagawa Japan; Tokyo Japan; Tokyo Japan; Kanagawa Japan
Problem: The objectives of this study were to consider whether psychological stresses were associated with the expression and genetic variations of Heat Shock Protein 70 (HSP70) in Meniere’s disease. Methods: Fifty consecutive patients with Meniere’s disease and twenty healthy donors as control ware enrolled in this study. Single Nucleotide Polymorphism (SNP) analysis was performed making use of Masscode_ system (Shimadzu Biotech) after DNA of these blood samples was extracted using a DNA extraction kit (PAX gene DNA blood kit, Qiagen). The expression of HSP70 and HSF1 in mRNA levels was examined with RT-PCR after tRNA was extracted using a RNA extraction kit (PAX gene RNA blood kit, Qiagen). Profile of mood states (POMS) was used in order to measure the level of psychological stress. Results: The genotypes of the polymorphism HSPA1L110 and 190 were confirmed in Meniere’s disease. The HSPA1L genotype G/C was associated with psychological stress and the number of attach of Meniere’s disease. The expression of HSP70 was induced by a wide variety stresses
including psychological stress, arteriosclerosis and inflammation. On the contrary, the expression of HSP70 was reduced by depression, ageing and diabetes. The HSPA1L genotype G/C induced the expression of HSP70 at mRNA levels. POMS show that an attack of Meniere’s disease was related to stress. Conclusion: These results suggest that genetic variations of HSP70 gene and a wide variety of stresses including psychological stress may contribute to an attack of Meniere’s disease. Significance: Our data indicated the importance of HSPA1L genotype G/C and psychological stress in Meniere’s disease.
R522 Changes in Chinchilla Vestibular Neuroepithelia after Intratympanic Gentamicin Treatment Lee Ching Wu Anderson, MD (presenter); Timo P Hirvonen, MD; Mohamed Lehar, MD; Casey C. Vogelheim; John P Carey, MD Baltimore MD; Helsinki Finland; Baltimore MD; Marquette MI; Baltimore MD
Problem: Single-dose intratympanic gentamicin is used to alleviate vertigo in patients with Me´nie`re’s disease. While known as “chemical labyrinthectomy,” intratympanic gentamicin does not stop spontaneous vestibular afferent firing, although sensitivity to vestibular stimuli is markedly reduced (Hirvonen et. al., 2002). The purpose of this study was to investigate the specific qualitative and quantitative effects of single-dose intratympanic gentamicin on vestibular neuroepithelia. Methods: Adult chinchillas received a single, unilateral intratympanic gentamicin injection (26.7 mg/ml, 30 min exposure); the contralateral ears served as controls. Animals were sacrificed and fixed either 14-28 days (early) or 3 months (late) post-treatment. Semicircular canal cristae and utricular maculae were sectioned for light and electron microscopy. Results: Median vestibular hair cell nuclei per transverse section was reduced by 53% in treated cristae (p⫽0.004) and 43% in treated utricular maculae (p⫽0.04), with loss of nearly all type I hair cells. Neuroepithelial height was reduced by 21% (p⫽0.004). Median vestibular afferent bouton number was unchanged (p⫽0.2). Median vestibular efferent ending number in the late group was reduced by 48% (p⫽0.04). Median ribbon synapse number was reduced by 48% (p⫽0.008). Of the hair cells remaining after intratympanic gentamicin treatment, there was a 66% decrease in the proportion of hair cells bearing stereociliary bundles (p⬍0.001). Conclusion: A single intratympanic gentamicin treatment does not create a complete labyrinthectomy. Rather, some hair cells and their synaptic specializations are preserved, which may provide the synaptic input to maintain spontaneous firing of vestibular nerve afferents. Significance: Preservation of spontaneous firing after intratympanic gentamicin treatment may decrease the adaptive
POSTERS
P132
Otolaryngology– Head and Neck Surgery August 2005
Otolaryngology– Head and Neck Surgery Volume 133 Number 2
R523 Evaluation of Quality of Life after Intratympanic Gentamicin for Me ´ nie ` re’s Disease Animesh Samar Banerjee, MD MS FRCSI (presenter) Newcastle Upon Tyne United Kingdom
Problem: To evaluate quality of life after Intratympanic Gentamicin for Meniere’s disease Methods: This retrospective study included all patients diagnosed of Meniere’s disease according to AAO-HNS criteria (refractory to medical management), undergoing Gentamicin labyrinthectomy in this unit over the preceding three years. Other causes of hearingloss were ruled out as all patients underwent MRI scan, ENG and Sway Magnetomety. Patients underwent gentamicin infiltration at concentration of 2mls of 30mg/ml & reviewed 6 weeks later with repeat injection if no benefit. Six months after their last follow up, they were sent GBI questionnaire. Twenty one questionnaires were posted, response rate was 81%. Results: As per the responses received, total benefit of intratympanic gentamicin injection was found to be ⫹30.3. Three components of GBI were analysed separately and it was found that general benefit was maximum (⫹33.3) followed by physical benefit (⫹28.1) and social benefit (⫹21.6) Conclusion: This study suggests that gentamicin definitely improves QoL in patients with Meniere’s disease and should be the first line of treatment if medical management fails. Significance: This study suggests that gentamicin definitely improves QoL in patients with Meniere’s disease and is relatively safe in preservation of hearing. It should be the first line of treatment if medical management fails R524 Anatomy of the Approach to the Petrous Apex Through the Superior Semicircular Canal Hamid R Djalilian, MD (presenter); Gina D Jefferson, MD; Helen Xiao-ou Xu, MD Los Angeles CA; Los Angeles CA; Los Angeles CA
Problem: The goal of this study is to use high resolution CT imaging to measure the means and ranges for the surgical approach to the petrous apex through the crura of the superior semicircular canal (SCC). Methods: High-resolution CT images of the temporal bone 1.0mm apart were obtained. Identical head position was insured using fixed landmarks. All patients were 18 years of age or older. Twenty of the 116 temporal bones had pneumatiza-
tion of the petrous apex and were examined for the study. Films were read by a neurotologist and neuroradiologist for evidence of abnormalities. Measurements were made using the standard PACS (picture archiving and communication system) measurement software. Results: Seven (35%) of the 20 temporal bones had air cells between the crura of the SSC. The mean anteriorposterior (AP) dimension of the intercrural space of the SSC was 3.67⫹/-0.31mm. The mean superior-inferior dimension of the approach was 3.59⫹/-0.31mm. When air cells were present in the intercrural space, the dimensions of the approach increased to 3.93⫹/-0.61mm for the AP dimension and 3.91⫹/-0.66mm for the superior-inferior dimension. Conclusion: Our study of 20 temporal bones provides the surgeon with the mean and ranges of the dimensions of the petrous apex approach through the crura of the SSC. These measurements show that this approach is anatomically possible for drainage of petrous apex cholesterol granulomas with minimal risk to the SSC by traversing the intercrural space. Resection of petrous apex lesions is probably not possible given the small intercrural space. Significance: This study allows the clinician to understand the dimensions and plausability of the surgical approach to the petrous apex through the crura of the superior semicircular canal. R525 Capping of the Third Window: A Five-Year Review of Superior Canal Dehiscence Syndrome Nathan Wayne Hales, MD (presenter); James E Saunders, MD Oklahoma City OK; Oklahoma City OK
Problem: Superior canal dehiscence (SCD) syndrome consists of vestibular and audiologic signs and symptoms, as well as bony dehiscence over the superior semicircular canal (SSC) on temporal bone CT. Medical and surgical treatments including SSC ablation and plugging have been reported. Nevertheless, several unresolved issues remain including the constellation of symptoms considered diagnostic, the pathophysiology of certain clinical features such as self-audible eye movements, and the optimal surgical technique. Methods: A retrospective review of eight patients with signs, symptoms, and imaging findings consistent with the diagnosis of SCD are presented. These findings will be compared with previous reports of SCD. The medical and surgical management will also be presented including a technique of capping the SSC, without ablation or plugging, intended to preserve SSC function. Results: The average age was 46 years old. No prior history of related trauma or infection was identified. No familial pattern was identified. The four most common presenting symptoms were: noise and pressure-induced dizziness, roaring tinnitus, pressure sensation, and hearing loss. A significant number of patients had self-audible eye move-
POSTERS
burden for the central vestibular nuclei in patients compared to surgical labyrinthectomy. Support: Supported by NIDCD R03 DC005700, K23 DC00196-01, R01 DC02390, T32 DC00027, P30 DC05211, grants from the Finnish Medical Foundation, Finnish Academy, and American Academy of Otolaryngology-Head and Neck Surgery Foundation.
Research Posters P133