Drugs inducing hearing loss, tinnitus, dizziness and vertigo: an updated guide.

OBJECTIVE: The awareness of audio-vestibular side effects of drugs, such as hearing loss, tinnitus, dizziness and vertigo, has widely increased in the recent years. The present guide represents an update of the previous documents published by the authors in 2005 and 2011 on drug-induced ototoxicity and vestibulotoxicity. MATERIALS AND METHODS: The authors performed a comprehensive analysis of audio-vestibular side effects of commercially available drugs based on the British National Formulary, a pharmaceutical reference book that contains a wide range of useful information and advice on prescription and pharmacology. RESULTS: Commercially available drugs and their active principles have been classified based on their audio-vestibular side effects, as reported by the pharmaceutical companies and/or health agencies. Drugs have been categorized based on the field of application, the therapeutic indication and the pharmacological properties. CONCLUSIONS: General practitioners, otolaryngology, neurology and audiology specialists should be aware of possible audio-vestibular side effects of drugs, such as hearing loss, tinnitus, dizziness and vertigo. The present guide represents a practical tool to rapidly identify potential audio-vestibular side effects of drugs as reported by the pharmaceutical companies and/or health agencies.

When alarm bells ring: emergency tinnitus.

OBJECTIVE: The aim of this study is to develop a diagnostic-therapeutic algorithm for those suffering from tinnitus who seek emergency aid. MATERIALS AND METHODS: A literature review has been performed on articles from the last 30 years. RESULTS: It is important to activate medical or surgical diagnostic and therapeutic strategies, in order to safeguard and rehabilitate the various functions affected. Psychiatric comorbidity is the most frequent pathological condition of those with serious or catastrophic tinnitus. In these cases, mortality risk is linked to suicide, morbidity to tinnitus-correlated distress. CONCLUSIONS: Tinnitus, mainly linked to loss of hearing, is a frequent symptom among the population at large. About 7% of those affected by tinnitus turn to their doctor to solve their problem, while between 0.5 and 2% request urgent medical assistance. Their cry for help may be the result of an acute onset of tinnitus or the rapid impairment of an already chronic condition. Tinnitus is not considered an urgent ear, nose and throat (ENT) condition by the Associazione Otorinolaringologi Ospedalieri Italiani (AOOI) [Italian Association of Hospital ENT], even though there are many pathological conditions, sometimes serious, associated with tinnitus and emergency action is necessary to reduce the risk of morbidity and mortality.

Early diagnosis of hearing loss: otoacoustic emissions evoked by distortion products and pure-tone audiometry: Preliminary findings.

OBJECTIVE: Literary studies underline the effectiveness of distortion product otoacoustic emissions (DPOAEs), which are not affected by the collaboration of the subject examined, in the early diagnosis of hearing loss. Aim of the study is to compare the objective technique of DPOAEs with respect to the pure-tone audiometry in early diagnosis of hearing loss. MATERIALS AND METHODS: The clinical research was carried out on 852 workers. All subjects underwent pure-tone audiometry, tympanometry and distortion products. RESULTS: The results show: a) a prevalence of subjects with impaired DPOAEs higher than the prevalence of subjects with impaired audiometries in the studied samples; and, after division by gender: b) a prevalence of subjects with impaired DPOAEs higher than the prevalence of subjects with impaired audiometries only in men; c) a prevalence of impaired DPOAEs and of impaired audiometries in men higher than in women. CONCLUSIONS: The results suggest the higher effectiveness of DPOAEs compared to pure-tone audiometry in making an early diagnosis of hearing loss.

Deafness in Italy: an epidemiological and socio-demographic study.

OBJECTIVES: Hearing loss is very common in our society, but epidemiological data on deafness in Italy is lacking. A.I.R.S. onlus (Italian Association for Research on Deafness) yearly launches the National Day for the Fight Against Deafness (NDFAD). During this events, that are held every year, it is possible to perform a free hearing test in all the facilities that have joined the initiative throughout Italy (240 hospitals joined in 2011). AIM: to report data collected throughout the "A.I.R.S. National Day for the Fight against Deafness" of the last years, focusing in particular but not only on audiometric outcomes. METHODS: demographic and social data, as well as audiometric outcomes, was collected on forms that have been subsequently stored in a on-line database and analyzed with MySQL and Microsoft Excel. CONCLUSIONS: This data are important in order to describe the "hearing health" of the Italian population, and is a first step towards creating a database with epidemiological and preventive aims, a strongly felt need both at national and at regional level.

Pharmacological drugs inducing ototoxicity, vestibular symptoms and tinnitus: a reasoned and updated guide.

The present work on drug-induced ototoxicity, tinnitus and vertigo represents the update and revision of a previous guide to adverse drug reactions for italian physicians (2005). The panorama of drug-induced side effects causing ototoxicity or symptoms such as tinnitus or dizziness and vertigo has enlarged in recent years, thanks to a better knowledge and a more specific attention of pharmaceutical firms and drug-control institutions. In daily clinical practice, there is a need for the family physician and the ENT specialist or audiologist (also in consideration of the possible medico-legal implications) to focus the attention on the possible risk of otological side effects. This would allow a clinical risk-benefit evaluation, weighing the possible clinical advantage in their field of competence against possible otological side-effects. The list of active ingredients and drugs is subdivided in categories based on their audiological and otoneurological side-effects, that have been signaled by the drug companies and/or ministerial notes. Drugs have also been subcategorized with regards to the field in which they are applied, the therapeutic indications and the clinical behaviour. They have also been organized in alphabetical order, for an easier consultation. The guide above, even if initially conceived for being used in Italy, also presents a more general and international interest, expecially as for as the concepts of pharmacology and the features of the active ingredients are concerned. The guide is, therefore, useful as for as we are concerned to any physician, regardless of the country he/she operates in.

[An updated guide on drugs inducing ototoxicity, tinnitus and vertigo]. / Guida ed aggiornamento sui farmaci ototossici, tinnitogeni e vertigogeni.

The argument of the iatrogenic side effects of pharmacological origin that can cause ototoxic effects or only disacustic symptoms like the tinnitus, without consequent degenerative effects, is enlarged in these last years. It is because of the great knowledge based on the careful attention from the pharmaceutical institutions which are responsible for the control of medicines and drugs. In the medical practice and in that specialty field born the need to gather, also in consideration of the possible medico-legal implications, those elements which will suppose the risk of otologic side effects. This will allow the physicians to evaluate the possible clinical advantage of a treatment, in their own field of competence, balancing them with their possible side effects in the otologic field. For this purpose, we have elaborated some updated lists of drugs with possible side effects of ototoxicity, tinnitus and vertigo; furthermore, we considered these drugs as could theoretically have influence on the auditory neurochemical progressing since they have excitatory or inhibitory action on the neurotransmitters and their receptors, but not signaled by the sources of institutional information.

Early diagnosis of endolymphatic hydrops with distortion. Product otoacoustic emissions.

The present investigation was specifically designed to evaluate the ability of the glycerol test combined with pure-tone audiometry, distortion-product otoacoustic emissions (DPOAEs) to diagnose endolymphatic hydrops early and to identify patients who may evolve toward Meniere's disease. This investigation consisted of 43 consecutive patients with daily episodes of tinnitus with duration exceeding few hours or with continuous tinnitus who received no treatment. These were the unique symptoms reported by the patients. Each patient underwent glycerol testing measured with conventional pure tone audiometry and with distortion product otoacoustic emissions (DPOAEs). For the traditional pure-tone glycerol test a hearing improvement of at least 10 dB, at the lower two or three frequencies (125,250 and 500 Hz) was judged as positive result. For the DPOAEs glycerol testing, a smaller positive difference (5 dB) for at least three frequencies was interpreted as a significant fluctuation. Twenty four patients showed negative glycerol test both with pure tone audiometry and DPOAEs. In 7 cases the improvement was concurrently observed. In 9 patients post-glycerol changes appeared only in the DPOAEs outcomes. Finally the remaining three patients had two different patterns. Two had different ameliorations of the DPOAEs and pure-audiometry on the left and right sides respectively, and in the last one only post-glycerol, audiograms recovered. The present study re-confirms the potentiality of DPOAEs associated with glycerol test in diagnosing endolymphatic hydrops precociously. The possibility of these patients degenerating into Meniere's disease should not be underestimated.

Diagnóstico precoz del hydrops endolinfático con emisiones otoacústicas con productos de distorsión / Early diagnosis of endolymphatic hydrops with distortion-product otoacoustic emissions

La presente investigación fue diseñada específicamente para evaluar la eficacia del test del glicerol combinado con audiometría tonal y las emisiones otoacústicas con productos de distorsión (DPOAEs) para diagnosticar precozmente el hydrops endolidnfático e identificar los pacientes que pueden evolucionar hacia la enfermedad de Ménière. Esta investigación se basa en 43 pacientes con episodios diarios de acúfenos con duración superior a varias horas o con acúfenos continuos. Estos eran los únicos síntomas referidos por los pacientes. Cada paciente se sometió al test del glicerol medido con audiometría tonal convencional y con productos de distorsión. Para el tradicional tono puro test del glicerol una mejoría de por lo menos 10 dB en dos o tres frecuencias graves (125,250 y 500 Hz) fue juzgada como un resultado positivo. Para la DPOAEs test del glicerol una diferencia positiva menor (5dB) para al menos 3 frecuencias fue interpretado como una fluctuación significativa. Veinticuatro pacientes presentaron un test del glicerol negativo en ambas pruebas tono puro y DPOAEs. Finalmente los 3 pacientes restantes presentaron patrones diferentes. Dos tuvieron mejorías en las DPOAEs y en la audiometría tonal del lado izquierdo y derecho respectivamente y el último sólo mejoró el audiograma postglicerol. El presente estudio reconfirma la potencialidad de las DPOAEs asociadas al test de glicerol en el diagnóstico precoz del hydrops endolinfático. La posibilidad de que éstos pacientes degeneren hacia una enfermedad de Ménière no debe ser subestimada (AU)

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Medico-legal use of otoacoustic emissions in the audiological selection process for employment.

A 6-year experience of the Italian Air Force Medical Selection Centre in the audiological evaluation of candidates for employment is summarized. Otoacoustic emissions (OAEs) were introduced progressively from 1993 to analyse more effectively subjects affected with sensorineural hearing loss and reduce possible bias connected to standard audiometric tests. OAEs provided a useful tool to support pure-tone audiometry, providing more accurate audiological data. Finally, a reduction of medico-legal claims was observed in candidates undergoing OAE testing.

Distortion-product otoacoustic emissions and glycerol testing in endolymphatic hydrops.

OBJECTIVES/HYPOTHESIS: Aural fullness is a frequent symptom of endolymphatic hydrops. Its evaluation may provide valuable information on the initial stage of development of endolymphatic hydrops. STUDY DESIGN: The present investigation was specifically designed to ascertain the ability of the glycerol test, combined with pure tone audiometry and distortion product otoacoustic emissions (DPOAEs) testing, to diagnose endolymphatic hydrops early and to identify patients who may evolve toward Meniere's disease. For these purposes, patients who complained about aural fullness as their only audiologic symptom were selected. METHODS: This investigation consisted of 19 consecutive patients with unilateral or bilateral aural fullness who received no treatment. Each patient underwent glycerol testing measured with conventional pure tone audiometry and with both DPOAEs. For the traditional pure-tone glycerol test, a hearing improvement of at least 10 dB, at the lower two or three frequencies (125, 250, and 500 Hz), was judged as a positive result. For the DPOAE glycerol test, a smaller positive difference (5 dB) for at least three frequencies was interpreted as an ameliorative fluctuation. RESULTS: The outcomes of the glycerol tests (24 ears examined) showed variable patterns. Seven ears showed no significant changes of either the pure-tone audiogram or DPOAE. In seven other ears, the comparison of the traditional glycerol test and the DPOAE glycerol test indicated an improvement in both measures. Another seven ears showed negative glycerol tests, whereas DPOAE responses gradually recovered reaching levels significantly higher than those recorded before glycerol administration. The three remaining ears showed contrasting results. CONCLUSIONS: Patients with aural fullness in the absence of other associated symptoms may potentially be in the initial stages of Meniere's disease. This notion is confirmed by the present findings showing a high rate (58%) of positive glycerol tests in the selected patients. The importance of DPOAE testing is supported by their ability to detect minimal dysfunction, possibly representing endolymphatic hydrops that goes undetected by routine pure-tone audiometry.

Distortion product otoacoustic emmissions in Ménière's disease.

Distortion product otoacoustic emissions (DPOAEs) are an objective, non-invasive measure for evaluating outer hair cell (OHC) activity. In this study DPOAEs were measured in 70 patients affected by Meniere's disease (MD). In addition 58 out of 70 patients performed both an audiometric threshold evaluation pre- and postglycerol administration (i.e. glycerol test) and DPOAEs pre- and post-osmotic drug assumption. The purpose of this combined form of testing was to explore the effects of glycerol on the active non-linear mechanisms of the cochlea. More than 60% of the ears with MD emitted DPOAEs despite the presence of an average hearing threshold level above 40 dB (HTL). Changes in the DPOAE baseline measures were observed in 32.4% of cases after glycerol administration. Patients were divided in four groups according to the different pattern of DPOAEs shown after the glycerol test. In particular, three-quarters of cases showed a significant increase in DPOAE amplitude, one-quarter of patients, who initially did not express DPOAEs, eventually did after intake of the osmotic agent, while no decreased DPOAEs were observed in these series. The different expressions of DPOAEs should be associated with the evolutive phases of MD. In addiction, elucidation of the relationship between DPOAEs and the stages of MD was an outcome of this test.

DPOAE modifications induced by pure tone overstimulation in guinea pigs.

Distortion Product Otoacoustic Emissions (DPOAEs) shows a vulnerability to acoustic overstimulation that is easily detectable by changes in amplitude, frequency distribution and time course. The frequency-specific changes in DPOAE provide more information than the more general changes in click evoked otoacoustic emissions. In this work five anesthetized guinea pigs were examined for changes DPOAE after exposure to pure tones. The noise was a 110 dB SPL pure tones for 45 minutes and the fatiguing tone centered on the geometric mean (GM) of primaries or 2/3 of GM. The most measurable effects were obtained in the latter conditions. The main DP level reduction lasts about one hour after exposure, but the complete recovery is observable only after 24 hours. The frequency distribution of fatiguing effects on the DP- audiogram shows a remarkable fine tuning and a pattern like a low-pass filter. After four hours, in one guinea pig, it is observable an enhancement of the DP amplitude, compared to the pre-exposure level; in another guinea pig, a second overstimulation produced a more extensive and time-lasting effects than the first exposure.

Distortion-product otoacoustic emissions and glycerol on the guinea pig hydropic ear.

OBJECTIVE: The aim of the present work was to investigate the therapeutic effects of glycerol on the distortion-product otoacoustic emissions in guinea pigs in which experimental endolymphatic hydrops had been surgically induced. METHODS: Thirty albino guinea pigs were used. The experimental protocol considered three groups of guinea pigs (10 animals each). Group 1 received no drug treatment, while group 2 and 3 were given glycerol orally 0.75 and 0.50 g/kg of body weight once a day for 24 days. RESULTS: The animals treated with glycerol showed an improvement of the distortion-product emission responses in the middle frequencies. This effect was not observed in the higher frequency region. This effect was evident 7 days after glycerol administration in the guinea pigs treated with a dose of 0.75 g/kg. The 0.50 g/kg dosage gave evidence of ameliorating effects 14 days after treatment. CONCLUSION: Glycerol given orally resulted in an improvement of distortion-product otoacoustic emissions in the guinea pig. Further studies are necessary before the effect of such a treatment can be assessed in humans.

[Analysis of otoacoustic distortion products in a group of otosclerotic patients]. / Analisi dei prodotti di distorsione otoacustici in un gruppo di pazienti affetti da otosclerosi.

There is indication that middle ear pathologies can affect otoacoustic emissions (OAE) to varying degrees. In fact, since acoustic emissions are recorded in the outer ear duct, the energy transfer mechanisms both up and downstream of the middle ear must be intact. OAE distortion products (DP) enable one to analyze cochlear response by frequency and to verify the retrograde response as a function of frequency. In the present work this method was used to test otosclerosis patients. A group of 45 patients with otosclerosis was tested to determine whether the OAE-DP could be identified and measured. Subsequently the characteristics of these DPs were analyzed in a group of 18 subjects who had previously undergone stapedectomy. All the results obtained were compared with those from a control group of normal hearing subjects with normal emissions and free of any E.N.T. pathology. In approximately half of the cases (53%) in the otosclerosis patient group it was possible to detect clearly evident DPs. Obviously, the DP-Gram differed greatly and average amplitude was lower than those found in normal subjects. Indeed, there was no signal at all at the lower and middle frequencies reflecting a hearing loss typical of cases of otosclerosis. Most (58%) of the otosclerosis patients who had successfully undergone stapedectomy recorded valid DPs. The DP-Gram frequency range was much broader (750-4000 Hz) than in those who had not undergone surgery. Moreover the lower and mid frequency amplitudes were significantly better. The data obtained are quite encouraging and suggest that DP should be studied in depth in patients with otosclerosis.

[Experimental endolymphatic hydrops and distortion otoacoustic emission]. / Idrope endolinfatica sperimentale e prodotti di distorsione.

The present investigation was designed to measure distortion-product otoacoustic emissions (DPOAEs) in a group of guinea pigs with endolymphatic hydrops in order to obtain normative data in this particular field. The-DPOAE's results were compared with compound action potential (CAP) outcomes to analyze the value of DPOAE measurements in audiologic screening. Thirty albino guinea pigs were used. Recording sessions were performed before the hydrops and 10,17 and 24 days thereafter. DPOAE measurements showed specific patterns of alteration providing quantitative data of the severity of the impairment and the specific frequencies involved. The close relationship of the functional effects of hydrops on the results of CAPs and DPOAEs suggests the potential contribution of DP testing to monitor the progression of the cochlear dysfunction of the hydropic ear.

[Distortion products in Menière's disease]. / I prodotti di distorsione nella malattia di Menière.

Distortion Product Otoacoustic Emissions (DPOAEs) are elicited by simultaneous application of two tones to the ear canal. These emissions are a result of nonlinear mechanical characteristics of the cochlea at a specific point and have a precise mathematical relation with the frequencies of the two eliciting primary tones f1 and f2. This frequency-selective property of DPOAEs suggests that they should be regarded as useful monitor of localized cochlear function at any predetermined frequency. The present study was designed to investigate DPOAEs in patients with Menière's disease. DPOAEs were recorded before and after glycerol administration to verify if the fluctuation of the hearing threshold induced by this hyperosmotic agent causes selective changes in the activity of the outer hair cells. DPOAEs were present in patients in which the mean duration of the disease was shorter compared to those patients without measurable DPOAEs. An improvement of DPOAEs after glycerol intatte was observed in a half of our cases. The improvement of DPOAEs does not appear to be brought about by modifications of the auditory threshold induced by glycerol.

Suppression tuning characteristics of 2f1-f2 distortion product otoacoustic emissions.

The 2f1-f2 distortion product otoacoustic emission (DPOAE) is suppressed by a third tone following a frequency selective pattern and outlining tuning curves which are generally similar to neural and psychophysical findings. The most effective suppressor tone lies between f1 and f2; less suppressive effects are produced by an added tone that lies in the 2f1-f2 site. The slope of iso-suppression curves is much steeper on the higher flank than on the lower flank of the suppression curve (respectively 100-115 dB/octave and 25-35 dB/octave). A suppression fine structure can be observed in the region of the tip especially for higher DPs probably connected with the fine structure of distortion products and with the instability of cochlear activity. A saturation point, around 70 dB or more has been evidenced on the growth rate functions. Continuous and interrupted suppressor presentation can induce some differences in the responses. Suppression of DPOAEs can provide a wider knowledge on active non-linear mechanisms in the cochlea, and on frequency selectivity also in a clinical context.

Some effects of tonal fatiguing on spontaneous and distortion-product otoacoustic emissions.

Auditory fatiguing can be considered a suitable test to assess some cochlear mechanisms and diseases otherwise not easily detectable. Since spontaneous otoacoustic emissions (SOAEs) originate from active sources within the cochlea they show sensitive and early vulnerability to noise, displaying informative time-courses after overstimulation in the short (0-6 s) and in the long term (1-10 min) depending on the frequency of the fatiguing stimulus. Distortion product otoacoustic emissions too, in subjects with SOAEs, show interesting modifications after pure-tone exposure, detectable either on distortion product audiograms or in the growth functions. The modifications take place within a period of 5-7 minutes and strongly depend on the frequency of the fatiguing stimulus and on the closeness between SOAE and distortion product place. The data suggest that not only the interaction place between f1 and f2 has to be considered from a biomechanical and clinical point of view, but also the specific distortion product place on the cochlear partition.

Spontaneous otoacoustic emissions from normal human ears. Preliminary report.

The present paper resumes the results obtained from measurement of spontaneous otoacoustic emissions (SOAEs), in terms of rate of occurrence, frequency spectrum and intra- and intersubjective variability in 104 normal ears (52 subjects). SOAEs have been detected in 27 ears (26.0%) and in 16 subjects (30.8%); bilateral SOAEs have been observed in 11 subjects (68.8%). Frequencies of the strongest emissions ranged from 1 to 2 kHz (96.3%); amplitudes varied from 3 to 20 dB SPL above the background noise. Spectra were always very sharp and stable in frequency, less in amplitude. Present results agree well with the data available in literature.

Bilateral temporal lobectomy for late radionecrosis after radiotherapy for acromegaly. A case report.

A patient with right temporal radionecrosis was submitted to temporal lobectomy for acute intracranial hypertension developed two years after radiotherapy for a GH-secreting pituitary adenoma. Eight months later, a partial left temporal lobectomy was performed because of further radionecrosis. In both instances the cerebral radionecrosis had the clinical and radiological characteristics of a space-occupying lesion. Bilateral temporal lobectomy was followed by a particular psycho-neurological syndrome with bilateral cortical deafness.