Objective: To clarify whether gentamicin affects vestibular dark cells in guinea pigs and relieves patients of aural fullness with intractable Ménière's disease following intratympanic administration. Materials and Methods: Purified gentamicin-Texas Red (GTTR) was injected intratympanically in guinea pigs that were sacrificed at 1, 3, 7, 14 and 28 days. GTTR uptake was examined in hair cells, and transitional cells and dark cells in vestibular end-organs were examined. Specific attention was paid to its distribution in dark cells under confocal microscopy, and the ultrastructure of dark cells using electron microscopy, following intratympanic injection. Results: Dark cells in the semicircular canals showed weak GTTR uptake at 1, 3, 7, 14 and 28 days after intratympanic injection, with no significant differences at various time points after injection. However, the adjacent transitional cells demonstrated intense GTTR uptake that was retained for at least 28 days. Ultrastructural studies demonstrated negligible characteristics associated with apoptosis or necrosis in these dark cells. The tight junctions between dark cells showed no signs of disruption at 7 or 28 days after injection. Conclusion: Intratympanic gentamicin has little direct impact on vestibular dark cells. Clinical Application: A modified low-dose titration intratympanic approach was used in 29 patients with intractable vertigo and the clinical outcomes were followed. Aural fullness following intratympanic gentamicin injection was not relieved based on our subjective scales, demonstrated by no statistically significant difference between preinjection (4.16 ± 3.08) and postinjection (3.58 ± 2.93; p > 0.05) aural fullness scores. Vertigo control was achieved in 88% of patients, with hearing deterioration identified in 16% of patients. Intratympanic gentamicin administration might not lead to relief of aural fullness in patients with intractable vertigo, although it can achieve a high vertigo control rate with some cochleotoxicity.

Keywords:
Gentamicin, Intratympanic injection, Dark cells, Ménière’s disease, Aural fullness
1.
Brinson GM, Chen DA, Arriaga MA: Endolymphatic mastoid shunt versus endolymphatic sac decompression for Ménière's disease. Otolaryngol Head Neck Surg 2007;136:415-421.
2.
Büki B, Platz M, Haslwanter T, Jünger H, Avan P: Results of electrocochleography in Ménière's disease after successful vertigo control by single intratympanic gentamicin injection. Audiol Neurootol 2011;16:49-54.
3.
Campbell KCM, Harker LA, Abbas PJ: Interpretation of electrochochleography in Meniere's disease and normal subjects. Ann Otol Rhinol Laryngol 1992;101:496-500.
4.
Cohen-Kerem R, Kisilevsky V, Einarson TR, Kozer E, Koren G, Rutka JA: Intratympanic gentamicin for Meniere's disease: a meta-analysis. Laryngoscope 2004;114:2085-2091.
5.
Committee on Hearing and Equilibrium: Guidelines for the diagnosis and evaluation of Ménière's disease. Otolaryngol Head Neck Sur 1995;113:181-185.
6.
Cureoglu S, Schachern PA, Paparella MM: Effect of parenteral aminoglycoside administration on dark cells in the crista ampullaris. Arch Otolaryngol Head Neck Surg 2003;129:626-628.
7.
Devaiah AK, Dawson KL, Ferraro JA, Ator GA: Utility of area curve ratio electrocochleography in early Meniere's disease. Arch Otolaryngol Head Neck Surg 2003;129:547-551.
8.
Ferraro JA, Tibbils RD: SP/AP area ratio in the diagnosis of Meniere's disease. Am J Audiol 1999;8:21-28.
9.
Fiorino F, Pizzini FB, Barbieri F, Beltramello A: Magnetic resonance imaging fails to show evidence of reduced endolymphatic hydrops in gentamicin treatment of Ménière's disease. Otol Neurotol 2012;33:629-633.
10.
Fiorino F, Pizzini FB, Beltramello A, Barbieri F: Progression of endolymphatic hydrops in Ménière's disease as evaluated by magnetic resonance imaging. Otol Neurotol 2011;32:1152-1157.
11.
Gacek RR, Gacek MR: Comparison of labyrinthectomy and vestibular neurectomy in the control of vertigo. Laryngoscope 1996;106(2 Pt 1):225-230.
12.
Ge X, Shea JJ: Transtympanic electrocochleography: a 10-year experience. Otol Neurotol 2002;23:799-805.
13.
Harner SG, Kasperbauer JL, Facer GW, Beatty CW: Transtympanic gentamicin for Meniere's syndrome. Laryngoscope 1998;108:1446-1449.
14.
Iseli C, Gibson W: A comparison of three methods of using transtympanic electrocochleography for the diagnosis of Meniere's disease: click summating potential measurements, tone burst summating potential amplitude measurements, and biasing of the summating potential using a low frequency tone. Acta Otolaryngol 2010;130:95-101.
15.
Kumagami H, Nishida H, Baba M: Electrocochleographic study of Meniere's disease. Arch Otolaryngol 1982;108:284-288.
16.
Lee JH, Chiba T, Marcus DC: P2X2 receptor mediates stimulation of parasensory cation absorption by cochlear outer sulcus cells and vestibular transitional cells. J Neurosci 2001;21:9168-9174.
17.
Li H, Wang Q, Steyger PS: Acoustic trauma increases cochlear and hair cell uptake of gentamicin. PLoS ONE 2011;6:e19130.
18.
McFeely WJ, Singleton GT, Rodriguez FJ, Antonelli PJ: Intratympanic gentamicin treatment for Meniere's disease. Otolaryngol Head Neck Surg 1998;118:589-596.
19.
Minor LB, Schessel DA, Carey JP: Ménière's disease. Curr Opin Neurol 2004;17:9-16.
20.
Naganawa S, Sone M, Yamazaki M, Kawai H, Nakashima T: Visualization of endolymphatic hydrops after intratympanic injection of Gd-DTPA: comparison of 2D and 3D real inversion recovery imaging. Magn Reson Med Sci 2011;10:101-106.
21.
Nakashima T, Naganawa S, Sugiura M, Teranishi M, Sone M, Hayashi H, Nakata S, Katayama N, Ishida IM: Visualization of endolymphatic hydrops in patients with Meniere's disease. Laryngoscope 2007;117:415-420.
22.
Oudar O, Ferrary E, Feldmann G: Ultrastructural study of the semicircular canal cells of the frog Rana esculenta. Anat Rec 1988;220:328-334.
23.
Pender DJ: Gentamicin tympanoclysis: effects on the vestibular secretory cells. Am J Otolaryngol 1985;6:358-367.
24.
Pitovski DZ, Kerr TD: Sodium and potassium-activated ATPase in the mammalian vestibular system. Hear Res 2002;171:51-65.
25.
Roehm P, Hoffer M, Balaban CD: Gentamicin uptake in the chinchilla inner ear. Hear Res 2007;230:43-52.
26.
Sajjadi H, Paparella MM, Williams T: Endolymphatic sac enhancement surgery in elderly patients with Meniere's disease. ENT J 1998;77:975-982.
27.
Sala T: Transtympanic gentamicin in the treatment of Meniere's disease. Auris Nasus Larynx 1997;24:239-246.
28.
Sass K: Sensitivity and specificity of transtympanic electrocochleography in Meniere's disease. Acta Otolaryngol (Stockh) 1998;118:150-156.
29.
Schmid K, Strutz J, Gleich O, Kwok P: Localization of gentamicin uptake in the acutely isolated inner ear of the rat. Int J Physiol Pathophysiol Pharmacol 2011;3:71-87.
30.
Shea JJ Jr, Ge NN: Summating potential and action potential ratio in Meniere's disease before and after treatment. Am J Otol 1998;19:478-482, discussion 483.
31.
Wang Q, Steyger PS: Trafficking of systemic fluorescent gentamicin into the cochlea and hair cells. J Assoc Res Otolaryngol 2009;10:205-219.
32.
Wangemann P: K+ cycling and its regulation in the cochlea and the vestibular labyrinth. Audiol Neurootol 2002;7:199-205.
33.
Yamamoto M, Teranishi M, Naganawa S, Otake H, Sugiura M, Iwata T, Yoshida T, Katayama N, Nakata S, Sone M, Nakashima T: Relationship between the degree of endolymphatic hydrops and electrocochleography. Audiol Neurootol 2010;15:254-260.
34.
Yen PT, Lin CC, Huang TS: A preliminary report on the correlation of vestibular Meniére's disease with electrocochleography and glycerol test. Acta Otolaryngol Suppl 1995;520(Pt 2): 241-246.
35.
Zhai F, Liu JP, Dai CF, Steyger PS, Wang Q: Evidence-based modification of intratympanic gentamicin injections in patients with intractable vertigo. Otol Neurol 2010;31:642-648.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.