Intratympanic Gentamicin Injection Research Articles

Low dose intratympanic gentamicin for control of intractable vertigo

Background and Objectives: Intratympanic gentamicin therapy is an effective modality for control of vertigo in Meniere's disease (MD) and when given in low concentration (<30 mg/mL), once weekly minimizes its side effects like chronic vestibular insufficiency or hearing loss. We studied the efficacy of low dose interval intratympanic gentamicin therapy in control of intractable vertigo in MD and the postprocedure hearing loss. As gentamicin is vestibular end-organ selective and not specific for treatment of MD alone we studied its efficacy in non-Meniere's peripheral vertigo (NMPV) in patients with nonserviceable hearing in affected ear. Subjects and Methods: Our study included 13 patients with “Definite” MD and seven patients with NMPV. In MD group, one treatment series consisted of a maximum of 3 weekly intratympanic gentamicin injections of 0.3 mL (12 mg) of gentamicin. In NMPV group, the schedule was similar but dosage per injection was 0.5 mL (20 mg). Another similar series of injections were repeated for recurrences. Results: Significant reduction was noted in number of vertigo spells in both groups after treatment (P < 0.001). All the patients experienced either complete or substantial control (Class A or B) of their vertigo. The functional level scale had significantly improved posttreatment in both groups (P < 0.01). No significant worsening in hearing was noted in any of the patients in MD group. Interpretation and Conclusion: Low dose interval intratympanic gentamicin is a simple cost-effective office procedure for managing vertigo in patients with MD and in patients with NMPV and nonserviceable hearing.

Comparison the Efficacy of Intratympanic Injections of Methylprednisolone and Gentamicin to Control Vertigo in Unilateral Meniere’s Disease

Comparison the Efficacy of Intratympanic Injections of Methylprednisolone and Gentamicin to Control Vertigo in Unilateral Meniere’s Disease

Modified titration intratympanic gentamicin injection for unilateral intractable Ménière's disease.

This study looked into the efficacy of a modified titration protocol of intratympanic gentamicin injection (ITG) in the patients with unilateral intractable Ménière's disease (MD). Modified titration protocol of ITG at a low dose (20 mg/mL) was administered to 10 patients with definite unilateral intractable MD. After initial first two fixed ITGs on weekly basis, the patients might or might not be given any more injections, depending on the appearance of unilateral vestibular loss (UVL). ITG was terminated if the patients satisfied the criteria of UVL. All patients were followed-up for at least two years. The effects of ITG on the vertigo attack, functional level scores and postural balance were evaluated. Of the 10 cases, 8 showed the sign of UVL after receiving initial two ITGs and were not given any more intratympanic injections, and the other 2 patients were administered three ITGs. A two-year follow-up revealed that complete and substantial vertigo control was achieved in 9 cases, and limited vertigo control in 1 patient. Hearing level was lowered in 2 patients. The posture stability and functional level scores were improved. Our study showed that the modified titration protocol of ITG at a low dose could effectively control vertigo in patients with unilateral intractable MD.

Intratympanic injection in delayed endolymphatic hydrops

Conclusions: The present study showed that intratympanic dexamethasone injection (ITD) is a promising approach for the treatment of contralateral and ipsilateral delayed endolymphatic hydrops (DEH). Moreover, intratympanic gentamicin injection (ITG), as a chemical labyrinthectomy, is a simple alternative for controlling vertigo in patients with ipsilateral DEH. Objective: This study examined the effect of ITD or ITG on DEH. Methods: Fourteen patients with DEH completed the clinical and audio-vestibular evaluation. Among them, 10 cases (ipsilateral type: nine cases, contralateral type: one case) were treated with intratympanic injection. Four patients with ipsilateral DEH underwent ITG, five patients with ipsilateral type and one patient with contralateral type received ITD. All 10 cases were followed up for 8–48 months. Results: Complete and substantial vertigo control was achieved in four of nine ipsilateral DEH patients treated with ITG. In the other five ipsilateral cases who received ITD, two accomplished complete vertigo control and two had substantial control. In one case, the vertigo was not effectively controlled. One case of contralateral DEH underwent ITD and this case had complete vertigo control. The vertigo intensity, vertigo frequency, vertigo duration and the functional level scale after intratympanic injection was decreased significantly.

Evaluation of the effect of intratympanic injection of gentamicin for resistant cases of Meniere’s disease on hearing and vestibular functions

Abstract This study was performed to investigate the effect of a single minimal dose of intratympanic injection (IT) gentamicin on hearing and otolithic function, mainly on the utricle and saccule independently. Our study was performed on 10 patients with definite Meniere’s disease diagnosed according to AAO-HNS criteria and who had been showing resistance to medical treatment for more than 6 months with persistent vertigo affecting their lifestyle. IT of gentamicin was given under local anesthesia through direct perfusion in a single dose of 12 mg (0.3 ml of 40 mg/ml) unilaterally on the lesion side. Preinjection evaluation included history, otoscopy, formal pure tone audiometry (PTA), and tympanometry. In addition, cervical vestibular-evoked myogenic potential (cVEMP) and oVEMP were tested. One month after injection, PTA and both VEMP tests were again carried out. Data before and after injection were analyzed and correlated. No overall significant effect on hearing was found. IT gentamicin had significant effect on cVEMPs with 100% abolition, as well as a statistically significant effect on oVEMP with 70% abolition and distortion of the remaining 30%. In these remaining 30% latencies and amplitudes, there was no significant difference in values before and after injection. A 12 mg single dose of gentamicin can abolish otolithic function without affecting hearing.

Histopathologic Changes of the Inner ear in Rhesus Monkeys After Intratympanic Gentamicin Injection and Vestibular Prosthesis Electrode Array Implantation.

Bilateral vestibular deficiency (BVD) due to gentamicin ototoxicity can significantly impact quality of life and result in large socioeconomic burdens. Restoring sensation of head rotation using an implantable multichannel vestibular prosthesis (MVP) is a promising treatment approach that has been tested in animals and humans. However, uncertainty remains regarding the histopathologic effects of gentamicin ototoxicity alone or in combination with electrode implantation. Understanding these histological changes is important because selective MVP-driven stimulation of semicircular canals (SCCs) depends on persistence of primary afferent innervation in each SCC crista despite both the primary cause of BVD (e.g., ototoxic injury) and surgical trauma associated with MVP implantation. Retraction of primary afferents out of the cristae and back toward Scarpa's ganglion would render spatially selective stimulation difficult to achieve and could limit utility of an MVP that relies on electrodes implanted in the lumen of each ampulla. We investigated histopathologic changes of the inner ear associated with intratympanic gentamicin (ITG) injection and/or MVP electrode array implantation in 11 temporal bones from six rhesus macaque monkeys. Hematoxylin and eosin-stained 10-μm temporal bone sections were examined under light microscopy for four treatment groups: normal (three ears), ITG-only (two ears), MVP-only (two ears), and ITG + MVP (four ears). We estimated vestibular hair cell (HC) surface densities for each sensory neuroepithelium and compared findings across end organs and treatment groups. In ITG-only, MVP-only, and ITG + MVP ears, we observed decreased but persistent ampullary nerve fibers of SCC cristae despite ITG treatment and/or MVP electrode implantation. ITG-only and ITG + MVP ears exhibited neuroepithelial thinning and loss of type I HCs in the cristae but little effect on the maculae. MVP-only and ITG + MVP ears exhibited no signs of trauma to the cochlea or otolith end organs except in a single case of saccular injury due to over-insertion of the posterior SCC electrode. While implanted electrodes reached to within 50-760 μm of the target cristae and were usually ensheathed in a thin fibrotic capsule, dense fibrotic reaction and osteoneogenesis were each observed in only one of six electrode tracts examined. Consistent with physiologic studies that have demonstrated directionally appropriate vestibulo-ocular reflex responses to MVP electrical stimulation years after implantation in these animals, histologic findings in the present study indicate that although intralabyrinthine MVP implantation causes some inner ear trauma, it can be accomplished without destroying the distal afferent fibers an MVP is designed to excite.

Single intratympanic gentamicin injection in Ménière's disease: VOR change and prognostic usefulness.

Assess angular vestibular-ocular reflex (VOR) changes after treatment with intratympanic gentamicin (ITG) for Ménière's disease (MD) and impact on short-term follow-up. Prospective study. Patients submitted to ITG for unilateral MD. The gain VOR and the presence of compensatory saccades elicited by rapid head impulses were measured using the video head impulse test (vHIT). The study included 31 subjects (mean age: 59 years). Functional Level Scale (FLS) distributions were 35,5% (FLS3); 32,2% (FLS4); and 32,2% (FLS5). Mean follow-up was 21 ± 7 months. Multiple injections were needed in nine patients. VOR gain in the treated ear was significantly reduced in all subjects and for all the semicircular canals (paired samples t test; P < 0,05). Gain averages after treatment were 0,61 (superior); 0,69 (horizontal); and 0,47 (posterior). A horizontal canal VOR gain superior to 0,80 after treatment was associated with the need for a second gentamicin injection (Chi-square; P = 0,003). Gain asymmetry between the symptomatic and asymptomatic ear (GASM) was increased after treatment. The rate of vestibular function reduction was 47,9%; 26,0%; and 35,8% for the superior, horizontal, and posterior canals, respectively. According to the receiving operator characteristic curve, the amount of change in GASM must be greater than 7 in order to predict the avoidance of a second procedure (area under the curve [AUC] horizontal canal = 0,861) and the amount of vestibular function reduction in the pathologic ear in patients with a controlled disease must be greater than 17,8% (AUC horizontal canal = 0,843). When evaluated with the vHIT, intratympanic gentamicin changes in VOR seem to foresee short-term control of vertigo attacks. 4.

めまいの外科的治療

For the management of patients complaining of vertigo, less-invasive treatments should initially be selected. However, failure of conservative treatment necessitates consideration of more invasive procedures. These managements sometimes include surgical measures, which could be associated with some complications.For benign paroxysmal positional vertigo, canal plugging surgery may be a valid treatment option. In the case of Meniere’s disease, ventilation tube insertion, endolymphatic sac decompression, intratympanic gentamicin injection, vestibular neurectomy and vestibulotomy can be used for critical cases. In cases with superior canal dehiscence, surgical treatment (re-surfacing of middle cranial fossa and anterior semi-circular canal plugging) is the only treatment option that offers the opportunity for resolution of symptoms. Recently, surgery for small tumors of the cerebellopontine cistern have tended to be avoided, although certain cases do need surgery. Devices to compensate for vestibular deficit, some of which need surgical device insertion, are also under research and development. It is necessary for physicians to be aware about the treatment options, including surgical procedures, with their benefits and risks, for appropriate treatment of vertigo. At the same time, we should be cautious about the selection, evaluation and establishment of surgical treatment procedures.

Successful treatment of relapsed Ménière’s disease using selective serotonin reuptake inhibitors: A report of three cases

Patients with Ménière’s disease who have relapsed following endolymphatic sac surgery (EDS) or intratympanic gentamicin injection are occasionally treated with intratympanic gentamicin injections or revision surgery. However, there is a potential link between Ménière’s disease and anxiety or depression. The use of serotonin selective reuptake inhibitors (SSRIs) is likely be beneficial in the treatment of patients with Ménière’s disease. The aim of this report is to describe the benefits of SSRIs in patients with relapsed Meniere’s disease. Over the course of two years, three patients were treated for symptoms associated with Ménière’s disease with an SSRI (sertraline), with the complete resolution, or significant improvement, of symptoms. In these cases, the SSRI may have treated the associated morbidity and not Ménière’s disease itself. Ménière’s disease that appears to be resistant to typical otological treatment may not be just Ménière’s disease. Ménière’s disease may co-exist with three other conditions that are able to cause vestibular symptoms and respond to SSRIs: migraine-associated vertigo (MAV), panic disorders and chronic subjective dizziness (CSD).

Directional Plasticity Rapidly Improves 3D Vestibulo-Ocular Reflex Alignment in Monkeys Using a Multichannel Vestibular Prosthesis

Bilateral loss of vestibular sensation can be disabling. We have shown that a multichannel vestibular prosthesis (MVP) can partly restore vestibular sensation as evidenced by improvements in the 3-dimensional angular vestibulo-ocular reflex (3D VOR). However, a key challenge is to minimize misalignment between the axes of eye and head rotation, which is apparently caused by current spread beyond each electrode's targeted nerve branch. We recently reported that rodents wearing a MVP markedly improve 3D VOR alignment during the first week after MVP activation, probably through the same central nervous system adaptive mechanisms that mediate cross-axis adaptation over time in normal individuals wearing prisms that cause visual scene movement about an axis different than the axis of head rotation. We hypothesized that rhesus monkeys would exhibit similar improvements with continuous prosthetic stimulation over time. We created bilateral vestibular deficiency in four rhesus monkeys via intratympanic injection of gentamicin. A MVP was mounted to the cranium, and eye movements in response to whole-body passive rotation in darkness were measured repeatedly over 1 week of continuous head motion-modulated prosthetic electrical stimulation. 3D VOR responses to whole-body rotations about each semicircular canal axis were measured on days 1, 3, and 7 of chronic stimulation. Horizontal VOR gain during 1 Hz, 50 °/s peak whole-body rotations before the prosthesis was turned on was <0.1, which is profoundly below normal (0.94 ± 0.12). On stimulation day 1, VOR gain was 0.4-0.8, but the axis of observed eye movements aligned poorly with head rotation (misalignment range ∼30-40 °). Substantial improvement of axis misalignment was observed after 7 days of continuous motion-modulated prosthetic stimulation under normal diurnal lighting. Similar improvements were noted for all animals, all three axes of rotation tested, for all sinusoidal frequencies tested (0.05-5 Hz), and for high-acceleration transient rotations. VOR asymmetry changes did not reach statistical significance, although they did trend toward slight improvement over time. Prior studies had already shown that directional plasticity reduces misalignment when a subject with normal labyrinths views abnormal visual scene movement. Our results show that the converse is also true: individuals receiving misoriented vestibular sensation under normal viewing conditions rapidly adapt to restore a well-aligned 3D VOR. Considering the similarity of VOR physiology across primate species, similar effects are likely to occur in humans using a MVP to treat bilateral vestibular deficiency.

Inner ear insult ablates the arousal response to hypoxia and hypercarbia

IntroductionSudden Infant Death Syndrome (SIDS) remains the leading cause of infant mortality in Western societies. A prior study identified an association between hearing suppression on the newborn hearing test and subsequent death from SIDS. This is the first finding of an abnormality in SIDS cases prior to death. A following study identified that inner ear dysfunction precipitates a marked suppression of the hypercapnic ventilatory response (HCVR). Failure of arousal has been proposed to be a key component in SIDS. The objective of the present study was to assess whether inner ear dysfunction not only weakens the hypercapnic response, but also plays a role in suppressing the arousal response to suffocating gas mixtures. MethodsWild-type mice (n=28) received intra-tympanic gentamicin (IT-Gent) injections bilaterally or unilaterally to precipitate inner ear hair cell dysfunction. Three control groups (n=22) received intra-tympanic saline (IT-Saline) bilaterally or unilaterally (right or left), or intra-peritoneal gentamicin (IP-Gent). The body movement arousal responses to severe hypoxia–hypercarbia combined (5% CO2 in nitrogen) were tested under light anesthesia 8days following the administration of gentamicin or saline. ResultsAfter injections, the bilateral and unilateral IT-Gent-treated animals behaved similarly to controls, however the HCVR as well as the arousal movements in response to severe hypoxia–hypercarbia were suppressed in IT-Gent-treated animals compared to control animals (P<0.05). Thus the HCVR was significantly decreased in the bilateral (n=9) and unilateral IT-Gent-treated mice (n=19) compared to bilateral (n=7) and unilateral IT-Saline (n=9) control groups (p<0.05). Arousal movements were suppressed in the bilateral IT-Gent group (n=9) compared to bilateral IT-Saline controls (n=7, P<0.0001) and in the unilateral IT-Gent group (n=19) compared to unilateral IT-Saline controls (n=10, P<0.0001). DiscussionThe findings support the theory that inner ear dysfunction could be relevant in the pathophysiology of SIDS. The inner ear appears to play a key role in arousal from suffocating gas mixtures that has not been previously identified.

Preclinical and Clinical Studies of Unrelieved Aural Fullness following Intratympanic Gentamicin Injection in Patients with Intractable Ménière's Disease

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.

Intratympanic gentamicin treatment ‘as needed’ for Meniere’s disease. Long-term analysis using the Kaplan–Meier method

In recent years, several titration or on-demand protocols using low-dose repeated intratympanic (IT) gentamicin injections have been adopted for the vertigo control in unilateral medical refractory Menière's disease (MD). Because of the frequent recurrence and the need to treat the patients several times, it is difficult to strictly follow the 1995 AAO-HNS criteria to classify the results. The Kaplan-Meier analysis provides an effective and simpler method to address these concerns. We report the results of a long-term study (7 years) on a large population of MD patients (174) treated with on-request low-dose delayed IT gentamicin injections analysed using the Kaplan-Meier survival method. Effective vertigo control was obtained with a single injection in 40.2% of the patients (excellent responders) and with repeated injections (2-9) in 43.7% of the patients (moderate responders). Only six patients (3.5%) needed to be submitted to vestibular neurectomy because of the persistence of vertigo attacks (non-responders). A subgroup of 22 patients (12.6%) reporting a late recurrence of vertigo attacks after an initial vertigo-free interval lasting more than 2 years (short-term responders) were successfully treated with a further cycle of injections. In no cases, we observed significant signs of cochlear or vestibular toxicity. Kaplan-Meier survival analysis provided an excellent method for reporting treatment success or failure in patients followed for variable length of time with our kind of protocol.

Gentamicin‐induced bilateral vestibulopathy in rabbits

Bilateral vestibulopathy (BV) is a mostly persistent and disabling disorder causing dizziness, oscillopsia, and imbalance during locomotion. The animal model is a prerequisite for experimental investigation on prevention and treatment of this disorder. The aim of this study was to determine the vestibular dysfunction and histopathology in rabbits with gentamicin-induced BV. Prospective animal study in rabbits. We performed intratympanic gentamicin (ITGM) injections in 12 Lionhead rabbits. The injection was applied to each ear with a 3-day interval. The control group received injections of 0.9% normal saline. The animals were subjected to sinusoidal harmonic accelerations and open field tests for evaluation of the vestibular function before and after the procedures. We also determined histologic changes in the vestibular labyrinth 30 days after the first injection. One day after unilateral ITGM injection, the rabbits mostly showed ipsiversive head tilt, contralesional spontaneous nystagmus, ipsiversive circling behavior, and decreased gain of the vestibulo-ocular reflex (VOR) during ipsiversive rotation. The second injection to the contralateral ear improved the head tilt but induced marked reduction in the activities and the VOR gains in both directions. These changes persisted until the histologic study confirmed the loss of the hair and supporting cells, diminished nerve fibers, and thinning of the sensory epithelium of the cristae ampullaris and otolith organs in the ITGM group 1 month later. ITGM injection securely induced BV in rabbits without side effects such as nephrotoxicity. This rabbit model may be utilized for experiments on the prevention and treatment of BV.

The Effect of Intratympanic Methylprednisolone and Gentamicin Injection on Ménière's Disease

To compare the efficacy of intratympanic injections of methylprednisolone (ITMP) and intratympanic injections of gentamicin (ITG) to control the symptoms of Ménière's disease and to evaluate their effect on hearing level. A historical cohort study. Tertiary referral center. Eighty-nine patients affected by Ménière's disease were included in this study, of whom 47 were treated with ITG and 42 were treated with ITMP. Two periods of follow-up were considered: 0 to 6 months and 6 to 12 months after the intratympanic injections (ITI). Mean outcome measurements consisted of control of vertigo attacks, tinnitus, and aural fullness; pure-tone average (PTA); and speech discrimination score (SDS). The 2 groups had the same number of vertigo spells per month before ITI (P = .883). Six to 12 months after ITI, 82.9% of the ITG group and 48.1% of the ITMP group achieved complete control of vertigo (P = .004). There was better control of tinnitus and aural fullness with ITG than with ITMP (P ≤ .002). The 2 groups had a statistically significant difference in hearing level before ITI (P ≤ .001). This difference was no longer present 6 to 12 months after ITI (P > .05). Intratympanic injections of gentamicin are more efficient than ITMP in controlling the symptoms of Ménière's disease. The 2 groups ended up without a difference in hearing level after ITI. According to these findings, administrating ITMP to control Ménière's disease seems to be less beneficial than ITG.

Outcomes of Intratympanic Gentamicin Injection to Treat Ménière’s Disease

To investigate the outcomes of intratympanic (IT) gentamicin sulfate injection to treat intractable Ménière's disease (MD) using evidence-based methods. Data were retrieved from a MEDLINE search (January 1995 through January 2011). Selected were English-language articles presenting outcomes of IT gentamicin injection to treat MD that had a prospective study design and an evidence level of II or higher. The database was searched using Boolean combinations of the keywords intratympanic, gentamicin, and Ménière's disease. Dichotomous outcomes (success rate and total deafness) were expressed using a Mantel-Haenszel fixed-effects model. Pretreatment and posttreatment pure-tone audiometry results, and word discrimination scores were summarized using data synthesis techniques. A critical literature appraisal and meta-analysis shows that IT gentamicin injection can control vertigo in patients with MD who have limited hearing injury. The quality of research in this field has improved remarkably over the years. However, a large-scale randomized controlled trial is warranted to confirm the predictive factors for the effectiveness of IT gentamicin injection in treating MD.

Cochlear function in Ménière's disease

Objective: The authors assessed the effectiveness of therapy, common features of pure-tone audiograms, and results of non-invasive electrocochleography before and after mild inhibition of peripheral vestibular function by infrequent administration of single intratympanic gentamicin injections (ITPG) in patients with Ménière's disease (MD). Study sample: Sixty-two patients with Ménière's disease. Design: Retrospective study. Results: Out of 62 patients 65% received one injection, 24% two, 6% three, 3% five, and 2% six injections. Between injections, class A vertigo control was obtained after two weeks in all cases. Before ITPG, out of 62 pure-tone threshold audiograms 37 were ‘flat’. Average hearing threshold at 2 kHz was significantly better than that of 250, 500, and 0.75 kHz on the affected side. Conclusions: Hearing threshold in advanced MD is often flat with a characteristic small peak in the high frequency range, most frequently around 2–3 kHz. Should the complaints be intolerable, single injection ITPG-therapy may be safe and effective.

Odległe wyniki leczenia choroby Ménière’a za pomocą dobębenkowych wstrzyknięć gentamycyny

To estimate the results of treatment of Ménière's disease with intratympanic injections of gentamicin. 37 patients with defined, pharmacological treatment resistant Ménière's disease treated in Department of Otolaryngology and Laryngological Oncology of University of Medical Sciences in Poznań with intratympanic injections of gentamicin from 2001 to 2010 year. Patients were injected intratympanic with 0.3 ml (12 mg) of gentamicin once or few times with 7 days or longer breaks and a number of injections depended on the reaction of the inner ear. We estimated the patients' subjective feelings and results of equilibrium and hearing organ examination in early (3 months) and late (2 years) period after treatment. Complete control of vertigo (class A) was achieved in 84.6%, and complete and essential control (class A and B) in 96.1%. Hearing deterioration usually mild or moderate was observed directly after treatment in 16.2% and after 2 years in 23% patients. The results of pure tone audiometry showed deterioration of hearing in 16.2% (early) and 26.9% (late). In 1 patient hearing deterioration was essential. Intratympanic injections of gentamicin are effective and not troublesome method of treatment of pharmacological treatment resistant Ménière's disease. In most of patients hearing can be preserved, but they should be always informed about possible risk of hearing deterioration. The number of injections and breaks between them depends on the effect of therapy and of expectations of patients.

Tinnitus: From Traditional Concept to Challenges to Loosen the Gordian Knot

Tinnitus is a distressing symptom that affects 15% of the population. Persistent tinnitus can interfere with an individual’s ability to perform usual daily activities and can prevent individuals from getting enough sleep. Tinnitus can cause considerable psychological distress and can be incapacitating (9). Causes of tinnitus include aging, exposure to loud environmental noise, stiffening of the middle ear bones, Meniere disease, labyrinthitis, otitis media, mastoiditis, acoustic schwannomas, ototoxic drugs, and head injuries. The facts that there are many different forms of tinnitus with different, often multiple causes and that the pathophysiology is poorly understood are obstacles to finding effective treatments. Neurosurgeons are generally unfamiliar with long-term management of tinnitus. If a patient complains of persistent tinnitus, the neurosurgeon usually rules out tinnitus of vascular flow origin such as dural arteriovenous fistula and carotid stenosis. Exclusion of a small acoustic schwannoma is also important. When no organic abnormalities are found, the neurosurgeon usually sends the patient to an otolaryngologist for further management. Most otolaryngologists never send the patient back for neurosurgical treatment. Some neurosurgeons have performed microvascular decompression of the cochlear nerve for intractable tinnitus (2, 6, 13, 16). Various audiometric tests have been developed over the years to identify vascular compression of the eighth cranial nerve preoperatively. Many of these tests are no longer in use. Vascular decompression for tinnitus is less successful than vascular decompression for trigeminal neuralgia or hemifacial spasm. Improvement may take up to 1 year. The most likely explanations of failure are that vascular compression, although present, was not the cause of the patient’s tinnitus or that changes of the central nervous system by prolonged peripheral injury were irreversible. Drug treatments for tinnitus are aimed at either the cochlea using intratympanic injections of gentamicin, dexamethasone, or lidocaine or the brain. Benzodiazepines and anticonvulsants have been used, and antidepressants have been introduced more recently. This strategy resembles medical treatment of neuropathic pain in which, following almost complete abandonment of peripheral nerve blocks, antiepileptic drugs and antidepressants play an important role. The mechanism of neuropathic pain is considered to be neuroplastic changes of sensory functions in the central nervous system after small lesioning in the pain pathway, and some types of tinnitus can be a result of deafferentation in the auditory mechanisms. Despite significant recent progress in understanding of neural mechanisms of tinnitus, neurosurgeons seem to be uninvolved in the treatment of this condition. In late 1990s, Jeanmonod, a Swiss neurosurgeon, and his group proposed a hypothesis of thalamocortical dysrhythmia syndrome to explain various forms of positive symptoms after lesioning of the nervous system (7, 11, 12, 17). These positive symptoms include neuropathic pain, tinnitus, abnormal movements, epilepsy, and certain neuropsychiatric disorders. With electroneurophysiologic recordings during stereotactic operations, Jeanmonod found thalamocortical dysrhythmia phenomena in patients with positive symptoms. Since then, with the development of imaging and electrophysiologic studies such as functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS), various functional abnormalities in the brain have been identified in patients with tinnitus. Tinnitus is accompanied by a change in the tonotopic map of the auditory cortex (1). There is a highly positive association between the subjective intensity of tinnitus and the amount of shift in tinnitus frequency in the auditory cortex (i.e., the amount of cortical reorganization). This cortical reorganization can be shown by fMRI. A brain network involving limbic and other nonauditory

Bone conducted vibration activates the vestibulo-ocular reflex in the guinea pig

The aim of the study was: (a) to test whether short duration (6ms) 500Hz bone-conducted vibration (BCV) of the skull in alert head free guinea pigs would elicit eye movements; (b) to test whether these eye movements were vestibular in origin; and (c) to determine whether they corresponded to human eye movements to such stimuli. In this way we sought to establish the guinea pig as an acceptable model for testing the mechanism of the effect BCV on the vestibulo-ocular reflex. Consistent short-latency stimulus-locked responses to BCV were observed. The magnitude of eye displacement was directly related to stimulus intensity as recorded by accelerometers cemented onto the animal's skull. The strongest and most consistent response component was intorsion of both eyes. In lateral-eyed animals intorsion is produced by the combined contraction of the inferior rectus and superior oblique muscles. In humans the same pair of muscles acts to cause depression of the eye. To test whether the movements were vestibular we selectively ablated the vestibular endorgans: 3 of the 8 animals underwent a bilateral intratympanic injection of gentamicin, an ototoxic aminoglycoside antibiotic, to ablate their vestibular receptors. After ablation there was an overall reduction in the magnitude of eye displacement, as well as a reduction in the effectiveness of the BCV stimulus to elicit eye movements. The animals’ hearing, as measured by the threshold for auditory brainstem responses, remained unchanged after gentamicin, confirming that the cochlea was not affected. The reduced magnitude of responses after vestibular receptor ablation demonstrates that the eye-movement responses to BCV are probably caused by the stimulation of vestibular receptors, which in turn activate the vestibulo-ocular reflex.