Vestibulotoxicity as a consequence of systemically administered tobramycin in cystic fibrosis patients.

CONCLUSION: The reported prevalence of vestibulotoxicity (30.4%) in cystic fibrosis (CF) patients supports vestibulotoxicity screening in CF patients during or after tobramycin exposure. Prospective longitudinal investigation is required for a more specific evidence-based proposal. OBJECTIVE: To investigate the prevalence of tobramycin-induced vestibulotoxicity in CF patients, as it had not been investigated before. PATIENTS AND METHODS: In this observational cohort study, 23 CF patient volunteers from the Haga Teaching Hospital Adult CF centre who had been exposed to at least one treatment with systemically administered tobramycin were included. Subjective feelings of dizziness were measured using validated questionnaires and vestibular symptoms were assessed by physical examination. Electronystagmography (ENG) with caloric irrigation was used as the gold standard. RESULTS: Peripheral vestibular loss was found in seven patients (7/23 = 30.4%). Central vestibular loss was found in one patient. Analysis of the 19 completed questionnaires showed that 12 patients (12/19 = 63.2%) did not experience dizziness and 3 patients (3/19 = 15/8%) experienced specific vestibular symptoms. The results of the questionnaire could not predict the results of ENG with caloric irrigation. Physical examination showed no abnormalities in any patients. No age- or dose-related predictive factors were found.

Vestibular and optokinetic nystagmus in ketamine-anesthetized rabbits.

The aim of this work has been to analyze the modification of vestibular and optokinetic nystagmus in animals after administration of therapeutic doses of ketamine. Three healthy rabbits (two reds and one white), weighing between 2.5 and 3 kg, were submitted to electronystagmography recording. The rabbits, head blocked, were placed on a Tönnies rotatory chair in the middle of a rotatory cylindrical chamber, the internal area of which was covered with 32 black vertical contrasts. All the rabbits underwent rotatory vestibular stimulation by stop test and optokinetic stimulation. After each test and a rest period for the animals, we administered 10 mg/kg of ketamine and performed the same ENG workup. In the first (red) rabbit, we collected eye-movement data at 3 minutes and 40 minutes after the intramuscular injection of a single dose of ketamine (10 mg/kg). In the second (white) rabbit, we performed ENG recording with the animal under anesthesia for the entire time of the test; in the third (red) rabbit, we analyzed the optokinetic response, from the administration of the drug until the end of its effects. Our data highlight the action of the drug on the structures that control the ocular movements and led to the conclusion of the presence of a second feedback integrator.

Intratympanic gentamicin treatment after endolymphatic sac surgery.

CONCLUSIONS: Interval treatment with up to three intratympanic gentamicin injections once weekly effectively controlled vertigo while preserving hearing in patients with Ménière's disease and recurrent or resistant vertigo after saccotomy. OBJECTIVES: Recurrent or resistant incapacitating vertigo may occur after endolymphatic sac surgery (saccotomy) in patients with Ménière's disease. In these patients, revision saccotomy, vestibular nerve section or labyrinthectomy are the established treatment options. We advocate a once-weekly application of intratympanic gentamicin (12 mg) as an effective alternative in this group of patients. MATERIAL AND METHODS: Five patients (age range 39-65 years) with definite Ménière's disease according to the 1995 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria and incapacitating vertigo underwent gentamicin treatment after saccotomy. Control of vertigo and hearing preservation were the aims of treatment. The follow-up period ranged from 26 to 59 months. History and pure-tone audiometry were used to assess vertigo control and hearing, respectively. The frequency of vertigo in the 6-month period before gentamicin treatment ranged between 0.5 and four definitive episodes per month. Hearing stage (AAO-HNS criteria) before gentamicin treatment ranged between 2 and 4. Pre- and post-treatment pure-tone hearing thresholds at 0.5, 1, 2 and 3 kHz were compared by means of the Mann-Whitney U-test. RESULTS: Complete vertigo control (class A; AAO-HNS) and hearing preservation at 0.5, 1, 2 and 3 kHz were achieved.

Effect of edaravone on streptomycin-induced vestibulotoxicity in the Guinea pig.

OBJECTIVES/HYPOTHESIS: The effect of topical administration of edaravone to the inner ear was investigated in guinea pigs with streptomycin-induced vestibulotoxicity. METHODS: Vestibulotoxicity was induced in 20 animals by delivery of streptomycin into the inner ear through osmotic pump for 24 hours. Edaravone (n = 8, systemic administration group) or saline (n = 6, control group) was injected intraperitoneally once a day for 7 days or edaravone-soaked Gelfoam was placed on the round window before wound closure (n = 6, topical administration group). RESULTS: Yaw head tilt and spontaneous nystagmus were observed in all animals after the operation. The number of spontaneous nystagmus beats in the topical administration group was statistically less than that in other two groups at 12, 18, and 24 hours after the operation. CONCLUSION: The study results suggest that topical administration of edaravone better suppresses streptomycin-induced vestibulotoxicity than systemic administration.

Audiovestibular evolution in a patient with multiple sclerosis.

Multiple sclerosis is characterized by the presence of multiple plaques within the central nervous system, manifesting as remission and exacerbation of neurologic dysfunction over variable time courses. We present the case of a 20-year-old woman. Before treatment, her auditory brain stem response (ABR) test revealed bilateral prolongation. A caloric test showed canal paresis of the right ear and a normal response on the left. A vestibular evoked myogenic potential (VEMP) test displayed an absent response in the right ear and a delayed response in the left. A magnetic resonance imaging (MRI) scan demonstrated multiple diffuse high signal lesions in the hemispheres, brain stem, and cerebellum. Six months after treatment, the demyelinating plaques were shown to have resolved spontaneously on MRI. Recovery of caloric responses was anticipated. Bilateral prolongation of ABRs remained, but the VEMP test disclosed a normal response in the right ear and a delayed response in the left. Accordingly, in addition to MRI, caloric tests and ABR and VEMP tests are useful in monitoring the evolution of audiovestibular function in patients with multiple sclerosis.

Ménière's disease.

PURPOSE OF REVIEW: Ménière's disease is characterized by spontaneous attacks of vertigo, fluctuating sensorineural hearing loss, aural fullness, and tinnitus. The pathologic process involves distortion of the membranous labyrinth with the formation of endolymphatic hydrops. This review describes the pathogenesis and etiology as well as the diagnosis and treatment of Ménière's disease. RECENT FINDINGS: Initial management of Ménière's disease can involve a low-salt diet and a diuretic. Treatment with intratympanic injection of gentamicin can be beneficial when vertigo persists despite optimal medical management. Recent studies have shown that gentamicin reduces vestibular function in the treated ear, although complete ablation of this vestibular function is not typically required in order to achieve control of vertigo. SUMMARY: Vertigo is often the most debilitating symptom associated with Ménière's disease. Many treatment options exist for the management of vertigo. Intratympanic injection of gentamicin (low dose) can be used in patients for whom vertigo has not been controlled by medical measures. Ongoing research is providing a greater understanding of the effects of gentamicin on vestibular function and of the mechanisms through which gentamicin leads to control of vertigo.

Middle ear instillation of gentamicin and streptomycin in chinchillas: electrophysiological appraisal of selective ototoxicity.

The purpose of this study was to investigate selective vestibular ototoxicity of gentamicin and streptomycin in the chinchilla model. In total, 10 chinchillas underwent left middle ear instillation of one of three agents: gentamicin, streptomycin and saline. Electrophysiological data (otoacoustic emissions (OAEs), auditory brainstem evoked response (ABRs), and ice-water electronystagmography were recorded before and after instillation. Animals were sacrificed for temporal bone studies using scanning electron microscopy. Morphological changes in the cochlear and vestibular neuroepithelia were correlated with electrophysiological changes. Widespread ipsilateral cochlear and vestibular neuroepithelial injuries were observed and correlated with loss of OAEs, ABRs and ice-water caloric response. This study provides no evidence of selective vestibular ototoxicity of gentamicin or streptomycin. Morphological damage correlates with, but precedes loss of electrophysiological parameters. Chinchillas, like other small mammals, may not be an ideal model for the study of human ototoxicity.

Objective evaluation of the effect of flunarizine on vestibular neuritis.

OBJECTIVE: To determine whether vestibular autorotation tests (VAT) would show significant differences in vestibular oculomotor reflex (VOR) parameters in vertiginous patients before and after treatment with flunarizine. STUDY DESIGN: Prospective study in a tertiary referral academic center. METHODS: Twenty-three patients (10 men, 13 women, mean age 45.57 years, mean length of disease 99.48 days, mean treatment 38.61 days), with vertigo due to vestibular neuritis, underwent VAT testing before and after treatment with 5 mg of flunarizine daily. RESULTS: The parameter improvement value (IV) resulted from subtracting posttreatment from pretreatment VAT numerical values. Regarding subjective improvement, 3 patients (13%) said they had none, 5 (21.7%) expressed moderate progress, 9 (39.1) considered the results satisfactory, and 6 (26%) became asymptomatic. The VAT results gave high positive IV for horizontal restriction, low positive for horizontal and vertical gains and horizontal asymmetry, and negative IV for horizontal phase and vertical restriction. Regarding the individual frequencies, horizontal and vertical gains improved in all the frequencies tested except one. The horizontal phase improved at low frequencies (2.0 and 2.3 Hz) and deteriorated from 2.7 to 3.9 Hz. Vertical and horizontal restriction showed both improvement and deterioration. Horizontal asymmetry displayed improvement from -0.01 at 2.0 Hz to 0.50 at 5.9 Hz, deteriorating from -0.41 at 9.0 Hz. CONCLUSIONS: Flunarizine is useful in the treatment of vertigo caused by vestibular neuritis. VAT is a valid instrument for the objective and quantitative evaluation of the vestibular-oculomotor reflexes.

[Vestibular toxicity of gentamycin in newborn infants]. / Zur Vestibulotoxizität von Gentamycin bei Neugeborenen.

BACKGROUND: Gentamicin known as ototoxic drug is routinely used for treatment of vital infections in neonatologic departments. The aim of the present study is to clarify whether gentamicin has a vestibulotoxic effect when used in therapeutic levels in the newborn phase. METHOD: Children were taken on the knees of the mother or relative sitting on an electronically driven rotating chair. The rotatory stimulation consisted of an undamped sinusoidal stimulus pattern which was performed in total darkness. Horizontal and vertical eye movements were recorded electronystagmographically. PATIENTS: The patient group consisted of 30 children aged between 3.1 and 32.9 months. These children had been treated with gentamicin during the newborn period. A group of 30 healthy children of similar age without gentamicin treatment was the control group. RESULTS: The statistical means of the nystagmus reactions during sinusoidal rotation were similar in both groups. No increase of spontaneous eye movements was seen in the patients or in the control group. CONCLUSIONS: Gentamicin is an important antibiotic for treatment of life-threatening infectious diseases, which acts less ototoxically in controlled therapeutic doses in newborns than in later childhood or in adults.

Click-evoked vestibulocollic reflexes in torticollis.

A total of 26 patients with torticollis were studied using a recently developed technique for recording vestibulocollic reflexes from the sternocleidomastoid muscles in addition to conventional caloric tests of vestibular function. Previous reports of abnormalities of vestibulo-ocular reflexes in these patients were confirmed with just fewer than half having significant canal pareses or directional preponderances (nine of 20 tested). In addition, there was a high incidence of abnormal click-evoked vestibulocollic reflexes (17 of 26 tested), which were not simply the result of prior treatment with botulinum toxin, nor due to unequal levels of muscle activation. In patients never previously treated with botulinum toxin (14 patients), the effect almost always consisted of suppressed responses in the sternocleidomastoid muscle ipsilateral to the direction of head turning. Because responses were not abnormal in all patients tested, and more commonly so in those with a history of torticollis of > or = 5 years (eight of nine patients) than in de novo patients, we suggest that the changes are more likely to be compensatory than causal.

Phenytoin for motion sickness: clinical evaluation.

Phenytoin has previously been shown to protect against motion sickness induced by Coriolis stimulation. The purpose of our series of investigations was to investigate further the efficacy of phenytoin for motion sickness prophylaxis and to gain insight into its mechanism of action. We tested participants with electronystagmography, off-vertical rotation, sea travel, and parabolic flight after they received phenytoin or placebo. Blood levels of at least 9 micrograms/mL were found to protect against motion sickness. Electronystagmography showed significant decreases in the gain of the vestibuloocular reflex in participants receiving phenytoin. Few side effects were seen with drug levels in the 9 to 15 micrograms/mL range. Phenytoin is an effective motion sickness countermeasure that may exert its effect through a combination of central nervous system and peripheral vestibular effects.

Reduction of streptomycin-induced acute and chronic toxicities.

The acute and chronic toxicities of streptomycin sulfate (SS) and of the streptomycin hydrochloride-calcium chloride complex (SCC) were compared. The LD50 determined in mice was significantly higher for SCC than for SS. Chronic toxicity was evaluated by recording the nystagmus induced by damped torsion pendulum in rabbits. SS and SCC treatments (200 mg/kg intramuscularly of absolute streptomycin base) decreased the duration, the maximal frequency, and the total number of beats of nystagmus. However, SCC-induced changes were significantly lower than SS-induced ones. The extent of the lesion in the crista ampullaris was evaluated by light and electron microscopy and was correlated with the electrophysiological findings. Because the authors also demonstrated that there are no differences in the antibacterial effects of these salts, SCC may have a place in long-term streptomycin treatment.

Cervicogenic headache: electronystagmography, perception of verticality and posturography in patients before and after C2-blockade.

Fourteen patients with cervicogenic headache (9F, 5M) with a mean age of 42.8 (29-58) years were examined, before and within two hours after unilateral anaesthetic C2-blockades, clinically as well as by means of electronystagmography, subjective visual vertical test and posturography. After C2-blockade, patients exhibited a slight gait deviation to the injected side without eye movement disorder, dysmetria or ataxia. Although in two of nine patients there was a small influence on lateral body sway on posturography, no specific pattern of abnormalities in eye-head-body coordination could be found before or after C2-blockades. Thus, there is no clinical evidence for a significant reproducible influence of the second cervical root on oculomotor or cerebellar function in cervicogenic headache. These findings confirm earlier data in animal experiments.

Effect of transdermally administered scopolamine on the vestibular system in humans.

In order to elucidate the effect of scopolamine on the vestibular system in humans, various experimentally-induced forms of nystagmus, i.e. caloric nystagmus, rotational nystagmus, optokinetic nystagmus, visual-vestibular interaction and optokinetic after nystagmus, were evaluated before and after the administration of two pieces of Scopoderm-TTS or placebo patches retro-auricularly. Scopolamine reduced the responses of both the caloric and optokinetic after nystagmus compared with the placebo. The possible action site of this drug is discussed.

[Streptomycin toxicity on dark cells of utricles in guinea pigs].

Thirty guinea pigs were divided into three groups. The first group received intramuscular injection of streptomycin sulfate 400 mg/kg/day for one week; the second group received the same dosage for two weeks; the third group served as the control. The cochlea was dissected after treatment and the utricle observed under electron microscope. The nystagmus lasted 11.3 sec. clockwise and 12.75 sec. counter-clockwise before treatment, 10.75 sec. and 9.25 sec. after one week and 6.0 sec. and 5.5 sec. after two weeks. Histopathologic study showed the normal dark cells in the control group. In the one week group, the dark cell remained in cuboidal shape. On the luminal surface of the cell were a few microvilli and invaginations which were in the process of forming pinocytotic vesicles. In the apical cytoplasm, the coated pinocytotic vesicles, vacuoles and rough endoplasmic reticula markedly decreased. The crest of mitochondria was blur, coalescent and vacuous. The plasmalemma in the lower part of the cell reduced. In the two-weeks group, the cells became squamous with less cytoplasm and organelle. There was no pinocytotic vesicles and vacuoles in the apical cytoplasm. The luminal membrane of the cells were bulging out into the cavity. In case the membrane ruptured, the cytoplasmic organelle run into the endolymphatic space and the cell dissolved and damaged. The morphological changes indicated that streptomycin damaged the cytoplasmic granules and the plasma membrane of dark cells. These cytologic characteristics of dark cells which engaged in the fluid transport were similar to those of the secretory cells in other organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Does administration of an aminoglycoside in a single daily dose affect its efficacy and toxicity?

Treatment efficacy, oto- and nephrotoxicity, and aminoglycoside pharmacokinetics were evaluated in a prospective, comparative, randomized clinical study of aminoglycosides given once a day or three times a day for severe infections. Sixty patients were treated with netilmicin or gentamicin 4.5 mg/kg bodyweight/day, either once a day or divided into three doses a day. The patients were allocated randomly to the different groups. The clinical effect was difficult to compare in the different groups, because of the small numbers of patients. Therapeutic failures were seen in seven patients (three after one and four after three doses per day). Two patients, one with Staphylococcus aureus endocarditis and one with streptococcal endocarditis, on netilmicin once daily and conventional high-dose therapy with a penicillin had positive blood cultures after five and seven days of treatment, respectively. Vestibular function and hearing acuity were examined by serial audiograms and electronystagmograms. In spite of extensive diagnostic evaluation, only two cases of ototoxicity were detected. One patient treated with gentamicin three times a day developed vertigo and a severe abnormality of her electronystagmogram. One young patient treated with gentamicin once daily had a slight bilateral reduction of hearing. Nephrotoxicity was mild and did not differ in the four treatment groups. This was the first investigation of a once-daily dosing regimen conducted in seriously ill patients with systemic infections. We could not demonstrate any evidence that aminoglycoside treatment once daily has greater oto- or nephrotoxicity than the traditional three times daily regimen.