Changes in the Three-Dimensional Angular Vestibulo-Ocular Reflex Following Intratympanic Gentamicin for Menieres Disease

JARO 03: 430±443 82002) DOI: 10.1007/s101620010053 JARO Journal of the Association for Research in Otolaryngology Changes in the Three-Dimensional Angular Vestibulo-Ocular Re¯ex following Intratympanic Gentamicin for MeÂnieÁre's Disease 1 1±3 4,5 1 JOHN P. CAREY, LLOYD B. MINOR, GRACE C.Y. PENG, CHARLES C. DELLA SANTINA, 6 7 PHILLIP D. CREMER, AND THOMAS HASLWANTER 1 1Department of Otolaryngology±Head and Neck Surgery, Johns Hopkins University, Baltimore, MD 21287, USA 2Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA 3Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA 4Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA 1 5Department of Biomedical Engineering, Catholic University of America, Washington, DC 20064, USA 6Eye and Ear Research Unit, Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Sydney, Australia 7Department of Neurology, ZuÈrich University Hospital, ZuÈrich, Switzerland Received: 19 June 2000; Accepted: 21 January 2002; Online publication: 26 March 2002 ABSTRACT these gain values and those for head thrusts that excited the contralateral canals were <2%. In contrast, The 3-dimensional angular vestibulo-ocular re¯exes caloric asymmetries averaged 40% 32%. Intra- 8AVOR) elicited by rapid rotary head thrusts were tympanic gentamicin resulted in decreased gains studied in 17 subjects with unilateral MeÂnieÁre's attributable to each canal on the treated side: disease before and 2±10 weeks after treatment with 0.40 0.12 8HC), 0.35 0.14 8AC), 0.31 0.14 8PC) intratympanic gentamicin and in 13 subjects after 8p < 0.01). However, the gains attributable to con- surgical unilateral vestibular destruction 8SUVD). tralateral canals dropped only slightly, resulting in Each head thrust was in the horizontal plane or in marked asymmetries between gains for excitation of either diagonal plane of the vertical semicircular ca- ipsilateral canals versus their contralateral mates: nals, so that each head thrust effectively stimulated HC: 34% 12%, AC: 24% 25%, and PC: 42% only one pair of canals. The AVOR gains 8eye velo- 13%. There was no difference in the AVOR gain for city/head velocity during the 30 ms before peak head excitation of the ipsilateral HC after gentamicin in velocity) for the head thrusts exciting each individual patients who received a single intratympanic injec- canal were averaged and taken as a measure of the tion 80.39 0.11, n = 12) in comparison to those function of that canal. Prior to intratympanic gen- who received 2±3 injections 80.42 0.15, n =5, tamicin, gains for head thrusts that excited canals on p = 0.7). Gain decreases attributed to the gentamicin- the affected side were 0.91 0.20 8horizontal canal, treated HC and AC were not as severe as those HC), 0.78 0.20 8anterior canal, AC), and 0.83 0.10 observed after SUVD. This ®nding suggests that 8posterior canal, PC). The asymmetries between intratympanic gentamicin causes a partial vestibular lesion that may involve preservation of spontaneous discharge and/or rotational sensitivity of afferents. Correspondence to: Dr. John P. Carey á Department of Otolaryngo- Keywords: vestibulo-ocular re¯ex 8VOR), MeÂnieÁre's logy±Head and Neck Surgery á Johns Hopkins Outpatient Center disease, vertigo, 3D eye movements, semicircular canals, á Room 6253 á 601 North Caroline St. á Baltimore, MD 21287- 0910. Telephone: 8410) 955-3403; fax: 8410) 614-7222; hearing loss email: [email protected] 430 CAREY ET AL.: AVOR after Gentamicin 431 INTRODUCTION The head thrust test has been quantitatively vali- dated using magnetic search coil recordings of eye When medical management fails to control intracta- and head movements. AVOR gain values near 1.0 ble vertigo in unilateral MeÂnieÁre's disease, options for have been demonstrated in normal subjects 8Aw et al. treatment include labyrinthectomy, vestibular neur- 1996a). Subjects with SUVD indeed have markedly ectomy, and intratympanic 8middle ear) injection diminished gains for head thrusts that would excite of gentamicin. Intratympanic aminoglycosides have the canals on the lesioned side 8Aw et al. 1996b). long been known to be effective in controlling vertigo Head thrusts in the planes of the vertical semicircular due to MeÂnieÁre's disease. Schuknecht 8using strep- canals likewise demonstrate hypofunction and can tomycin) and Lange 8using gentamicin) gave multi- even isolate hypofunction affecting only one canal ple intratympanic injections of these antibiotics each 8Aw et al. 1995a,b; Cremer et al. 1998, 2000; Minor day until patients developed dysequilibrium or until et al. 2001). caloric responses were abolished 8Schuknecht 1957; We used head thrusts in horizontal and vertical Lange 1976, 1989, 1995a,b). Vertigo was controlled canal planes to measure the AVOR gains in cases of in most of these patients 8100% in Schuknecht's unilateral MeÂnieÁre's disease before and after intra- series; 88% in Lange's), but the rates of sensorineu- lympanic gentamicin treatment, and we compared ral hearing loss attributed to the aminoglycosides the post-gentamicin gains with those from control were unacceptably high 862% and 48%, respectively). subjects who had complete SUVD. We found that Subsequent reductions in the number and frequency even a single dose of intratympanic gentamicin of doses have resulted in control of vertigo in 70%± caused marked decreases in the AVOR gains when 90% of patients and a reduction in the incidence of head thrusts excited any of the treated canals. For the sensorineural hearing loss 8Beck and Schmidt 1978; horizontal and the anterior canals, the asymmetries Odkvist et al. 1984; Nedzelski et al. 1992, 1993; Toth in gain between these canals and their contralateral and Parnes 1995; Murofushiet al. 1997; Hirschand mates caused by gentamicin treatment was signi®- Kamerer 1997; Rauch and Oas 1997; Minor 1999; cantly less than that caused by SUVD. These data Silverstein et al. 1999; Atlas and Parnes 1999). Most indicate that intratympanic gentamicin may be physio- recently, it has been shown that a single intratym- logically less destructive than SUVD, perhaps because panic injection of gentamicin is effective in the con- the spontaneous discharge rate and/or modulation trol of vertigo in most patients 8Freedman and Sparks with head motion are preserved in vestibular nerve 1997). afferents arising from the treated side after limited Our study addresses the effect of such low doses of injections of gentamicin. intratympanic gentamicin on vestibular function as measured by caloric tests and by the 3D angular vestibulo-ocular re¯ex 8AVOR) elicited by rapid rotary METHODS head thrusts in the planes of the semicircular canals. Subjects Halmagyiand Curthoys 81988) introducedthe head thrust test, demonstrating that subjects with complete Subjects with MeÂnieÁre's disease. Seventeen subjects 8G1± surgical unilateral vestibular destruction 8SUVD) on 17) were patients with ``de®nite'' unilateral MeÂnieÁre's one side fail to maintain visual ®xation on a target disease as de®ned by the 1995 criteria of the when the head undergoes a rapid rotation toward the American Academy of Otolaryngology±Head and lesioned side. The test relies on Ewald's second law Neck Surgery 8Monsell et al. 1995).1 The patients which speci®es that there is a greater effect from had experienced symptoms of vertigo, hearing loss in excitation of a semicircular canal than from inhibition the affected ear, tinnitus, and/or aural fullness for 5 of a canal 8Ewald 1892). When the head is horizon- 4 years [mean standard deviation 8SD), range = 3± tally rotated toward the intact side in the head thrust 15 years] prior to the intratympanic administration of test, the horizontal canal on the intact side is excited. gentamicin. Low-salt diets and diuretics failed to The usual±but small±contribution of inhibition from control their vertigo. Eight subjects were women and the canal on the lesioned side is missing, but the re- 9 were men, with ages ranging from 38 to 71 years sponse 8eye velocity) generated by the excited canal is 855 15, mean SD). All subjects gave informed suf®cient to yield a compensatory AVOR. However, consent for the 3D AVOR recordings through a pro- when the head is horizontally rotated toward the lesioned side, the horizontal canal on the intact side is inhibited. Without the large excitatory contribution from the horizontal canal on the lesioned side, the 1Two or more spontaneous episodes of vertigo lasting 20 min or longer, hearing loss documented with an audiogram on at least one asymmetry between excitation and inhibition be- occasion, tinnitus or aural fullness in the affected ear, other comes manifest, and the AVOR is noncompensatory. pathologies excluded 8Monsell et al. 1995). 432 CAREY ET AL.: AVOR after Gentamicin tocol approved by the Joint Committee on Clinical the hair cell, gentamicin levels rise with cumulative Investigation at the Johns Hopkins University School dosing for periods of several weeks 8Beaubien et al. of Medicine, the institution at which treatment 1995). 83) Both laboratory and clinical studies sug- and testing were performed. Patients were tested gest that increasing the total intratympanic dose of 0±2 days prior to the ®rst gentamicin treatment, aminoglycosides increases the risk of cochlear hair except patient G6 who was tested 31 days prior to cell damage 8Wanamaker et al. 1999) and the risk of the ®rst treatment. Post-gentamicin testing was profound sensorineural hearing loss 8Kaplan et al. performed 12±94 days after the ®nal gentamicin 2000). Complete control of vertigo was obtained treatment. after a single intratympanic injection of gentamicin Subjects with surgical unilateral vestibular destruction in 7 of the 8 patients. For one patient in whom 4SUVD). Thirteen subjects were tested as controls with vertigo was not controlled 8G15) by the single injec- known complete unilateral vestibular hypofunction tion, two further gentamicin treatments were given after surgical destruction of the peripheral vestibular at intervals of 3 and 2 months until vertigo was system on one side.

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