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This article provides a review of studies investigating the pharmacological treatment of tinnitus. Though success rates of 80% tinnitus control are reported with such treatment modalities as biofeedback [3] and tinnitus retraining therapy [4], these modalities of therapy are time consuming for providers and patients alike. Until recently, the lack of animal models for tinnitus has further limited our ability to define the role of pharmacological agents in preparation for clinical study. As a result, our objectives here are to review the basic and clinical science evidence for the pharmacological treatment of tinnitus, to assess for consensus on symptom definition and outcome reporting, and to chart a course for future efforts. We searched MEDLINE (1966-2005) for English-language studies combining the word tinnitus with the term medical treatment, pharmacologic , or pharmacological.
We considered evidence in light of study type, design, clarity, and applicability of findings. Tricyclic antidepressants decrease presynaptic reuptake of norepinephrine and serotonin, whereas selective serotonin reuptake inhibitors (SSRIs) decrease reuptake of serotonin only.
The results of clinical studies on antidepressants in the treatment of tinnitus are summarized in Table 1. The results of clinical studies of GABA receptor-binding pharmacological agents are presented in Table 2. No consistent symptom definition was identified in these studies, and all populations were essentially convenience samples from clinics or databases.
Studies addressing the use of misoprostol in the treatment of tinnitus are summarized in Table 3. The first study had essentially no symptom definition [23], whereas the most recent two were limited to subjective tinnitus of greater than 6 months' duration with fairly specific inclusion and exclusion criteria. The evidence linking various vitamin B deficiencies and treatments with tinnitus are largely anecdotal [7]. Zinc is an essential nutrient that can influence neurotransmission and is present in highest concentration in the human cochlea [31].
The two placebo-controlled trials of zinc were noticeably thorough with symptom definition, including laterality, constant versus intermittent, quality, pitch, association with disease process, and association with audiometric data. EGB761 is the most common isolate of Ginkgo biloba, one of the most ancient medicinal plants recently reported to increase body circulation and having benefits for vascular insufficiency and cognitive function [7].
To isolate subjects likely to respond to treatment, one study [38] started with an open trial of 80 patients, all of whom received treatment. Overall symptom definition was vague in these studies, and no study presented a systematic method by which to identify significant otological disease as a cause of tinnitus. Antidepressants likely have a role in the management of tinnitus concomitant with major depression or depressed symptoms and can help in ameliorating comorbidities in severe or chronic cases of tinnitus. GABA receptor-binding medications, such as benzodiazepines, appear to be reasonable candidates for tinnitus therapy, given the inhibitory role of GABA in the central nervous system. Of all the nutritional supplements, zinc has had the longest history and has been subjected to the most clinical study.
The results of studies on Ginkgo biloba as a whole tend to argue against any benefit for the treatment of tinnitus.
Given the likely wide range of potential causes of tinnitus, a thorough definition of the patient population must be established.
Once outcome measures are decided, a formal inquiry of statistical power should be reported to determine the required number of subjects in all treatment arms. Basic science models for tinnitus, though limited, should be used to guide more productive study of pharmacological treatments for tinnitus. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the US Department of the Navy, US Department of Defense, or the US Government. WE, THE EDITORS AND STAFF of the International Tinnitus Journal (ITJ), have lost a colleague and a friend, Dudley J. With all who were blessed to have known him, he shared his zest for life and his enjoyment of and pride in family and friends. He was born in Norwalk, Ohio, on July 20, 1938, a son of Mary Janet (Johnston) Rogers and Nathaniel Rogers. In 1974, he returned with his family to the Upper Valley, where he joined the Hitchcock Clinic. He was a physician dedicated to his patients, giving tirelessly of his time, providing compassionate care.
He was secretary and treasurer of the Grafton County Medical Society from 1978 to 1984, vice president in 1984, and president in 1985. He published dozens of professional papers, was a contributor to several chapters in books, and gave hundreds of lectures in his field. He was the current president of the Hanover Lions Club and a member of Church of Christ at Dartmouth College. In 1996, he climbed Mount McKinley, where he was responsible for saving the lives of several climbers who fell. I WAS UNBELIEVABLY SHOCKED and deeply saddened to find out about the unexpected passing of my old friend and colleague, Dudley Weider, MD.
Because of his physical fitness focus, it is so unexpected that he passed away suddenly in the midst of a routine vigorous exercise activity.
At the PMS meetings, Dud always asked the best questions and really enjoyed a deep and provocative exchange of ideas on all sides of a topic. Dudley was a founding member of the PMS and served on the board of directors since its inception. I am truly sorry that he will not be able to attend the twenty-fifth anniversary meeting of the PMS in Austria in March.
Dudley was the perfect combination of a true physician, friend, family man, surgeon, investigator, and personal resource. I HAVE BEEN FORTUNATE to have had the opportunity to know Dudley Weider, MD, on both a personal and a professional level. I had the privilege of going on several fishing trips with Dudley, during which I came to know him very well. The medical profession has prematurely lost an outstanding physician who still had much to offer. DUDLEY WEIDER has been a close friend since I met him at a Prosper Meniere's Society Meeting in Aspen. Dudley's caring nature won the trust of his patients as he sought treatments to meet their individual needs. Dudley's quiet presence and caring nature are still with us today, and it is a lesson I keep with me.
My contact with Dudley was usually made at the major spring and fall meetings, specialty meetings, and fishing trips. Tinnitus is associated with the most important symptoms in neurootology besides vertigo, nausea, and hearing loss.
Since about 1985, via vestibular evoked potentials (VestEP) and brain electrical activity mapping (BEAM), the Wurzburg Neurootology Group of Claussen et al.
For this study, we randomly selected a sample of 757 patients suffering from an endogenous tinnitus according to the tetrad of tinnitus differentiation described.
We followed with a thorough audiometric investigation to obtain measurements of the hearing threshold, the acoustic discomfort threshold, the calculation of the acoustic dynamics, tinnitus masking, impedanciometry, and stapedial muscle reflexes. In assessing the vestibulospinal pathways, we regularly applied craniocorpography (CCG) in the form of ultrasonographic computed craniocorpography (UCCCG).
The test results from our analyses helped us to demonstrate that these 757 patients were suffering from an endogenous tinnitus.
At the Neurootological Research Institute at Bad Kissingen, we recorded statistics from our 757 patients suffering from an endogenous tinnitus. After exploring the vertigo mechanisms, we analyzed the different sensations in hearing distortion in our patient sample (Fig.
Figure 20 shows our analysis of trigeminal nerve complaints: Although no patient reported trigeminal nerve disorders, the medical investigators found such disorders by direct inspection relative to patients' obtained medical history. The special set of questions regarding our patients' history dealt with specific neurological disorders (Fig.
Very well known is that after head and neck trauma, many patients complain of various types of tinnitus.
Cardiovascular diseases were very important background disorders for our neurootological patients. We also questioned our patients about diabetes mellitus and categorized these cases with respect to their therapy.
For this study, we randomly selected 757 tinnitus patients who reported that they felt better in a noisy environment. The question underlying this study is whether tinnitus is a monosymptomatic disease or is bound into a complex spectrum of complaints within a multisensory disorder.
We saw a very varied picture in the subjective descriptions of the quality of tinnitus sensations. Of background disorders, various cardiovascular diseases showed a high occurrence rate (Fig. All in all, we must conclude that our evaluations in studying our 757 cases demonstrate that the spectrum of subjective complaints is very complex and individually mingled. Overall, our evaluation of 757 patients with endogenous tinnitus posits that the most important accompanying general diseases are cardiovascular.
From all these patterns of interactive complaints, we also must conclude that endogenous tinnitus points to a "cybernetopathia" deriving from dysfunctions at various points of the statoacoustic and interrelated supportive neurosensory pathways. In otolaryngologists' offices, simple speech tests using monosyllabic words and two-digit numbers, such as the monosyllabic CID-W-22 Silberman and Hirsh Test [1] employed in the United States or the Freiburg Hahlbrock Speech Discrimination Test [2] employed in Germany, have proved to be very effective in routine examinations, as their designs are easily adapted to the average patient. The cocktail-party effect that affects these patientsor of which they generally complain-may reduce the perimeter of their speech discrimination capacity to a few centimeters between their ear and the person communicating with them. Several investigations have shown that ascending degeneration of the hearing nerve, as described by Spoendlin [3,4], is responsible for the cocktail-party effect as long as the central auditory functions remain intact. In the last decades, extensive experimental and clinical studies of the hearing organ in humans and animals have disclosed with growing exactitude the multistage functional efficiency of the auditory system regarding various damage and possible vulnerability criteria (Fig.1). Approximately 30 outer hair cells are supplied with a single afferent nerve fiber, whereas some 20 afferent nerve fibers are connected to a single inner hair cell.
Spoendlin [4] further proved that destruction of inner hair cells after overexposure to noise may cause an ascending degeneration of the hearing nerve-with devastating consequences for speech discrimination. Although the proposals for OAE measurements when examining functional disorders of the cochlear amplifier are explicit, the fact that failing OAEs also may indicate ascending degeneration has, until now, not been accepted clinically. As early as the 1950s, the selection capacity of the ear was interpreted by Schubert [12] as a specific performance of the inner ear, whereas such authors as Keidel [13] and Wedel [14,15] classified it as a central process. In view of the rather complicated, time-consuming, and not very practical procedures of Schubert's speech tests, we decided instead to develop further the simple Freiburg Hahlbrock Speech Discrimination Test used widely in otolaryngologists' offices and, to a large extent, corresponding with the American CID-W-22 Silberman and Hirsh Test, using monosyllabic words and two-digit numbers.
By calculating the test results as a function of nondistorted and distorted test data, we were able to set up, relatively quickly even during examination, a quantitative evaluation of the patient's actual speech discrimination capacity, comparable to real-life conditions even under aggravating circumstances, such as a noisy party. In the testing of persons with normal hearing, patients with conductive hearing loss or combined hearing impairments, and patients with sensorineural hearing loss, the reverberation ratio is pathological almost solely in persons with sensorineural hearing loss.
As can be seen in Figure 4, the reverberation ratios are significantly higher for sensorineural hearing impairments as compared to conductive hearing loss and normal hearing.
The development of modem yet, in many cases, rather extravagant hearing test methods allows a steadily growing insight into the localization of damage to the auditory system. Various other modem examination techniques, such as magnetic field audiometry, must be preceded by subtle audiometric examinations because only homogeneous patient cohorts allow conclusions as to specific alterations in the magnetic field and to the diagnostic value of the method [18].
The method seems to be of special advantage in cases in which an ascending degeneration and damage to the cortical selection centers are suspected.
Because the distorted-speech test combined with the obligatory speech discrimination test renders information both about pathological masked speech results and about pathological time-related signal-analyzing mechanisms, it is recommended for incorporation into every audiometric test battery as a basic component.
We auditorily stimulated patients affected by subjective tinnitus with broadband noise containing a notch around their tinnitus frequency. We recruited tinnitus sufferers from among patients attending the Oto-Rhino-Laryngology II Clinic of the University of Parma, Italy, in the period 2004-2006. We determined hearing sensitivity using tonal stimuli presented in octave steps, from 125 Hz to 8,000 Hz, and 1-dB increments.
The experimental pitch-matching test was performed shortly after the patient had performed the loudnessmatching test using pure tones as comparison stimuli. Conversely, in our study, an essential prerequisite for the correct application of the experimental acoustic therapy (notched broadband noise; see later) was the reliability (and repeatability) of the measurement of the tinnitus pitch. Our method was based on the classic pure tone-matching paradigm and consisted of two phases. During both the upward and downward sweeps, we stopped tone presentation every time the subject reported a match between the tone and the pitch of the tinnitus. The second phase (termed sequential binary choice) resembled the traditional 2AFC procedure. During this phase, a number of patients reported more than one tone as matching their tinnitus pitch. We should note that any procedure of tinnitus pitch assessment is subject to many errors owing to, for example, differences in the ability of subjects to compare and discriminate among tones, the uniqueness of the tinnitus sensation, or the presence of different types of tinnitus. The experimental design consisted of randomly assigning to each patient either the experimental sound therapy (WWN)* or one of the two control sound therapies (WN or Wa) following a double-blind procedure. We examined variation of the tinnitus parameters (F t , dB t ) over time for each patient by repeating measurements, ideally after 1, 3, and 6 months from the start of the therapy, following the same procedures of the first visit.
In addition, when the subject's tinnitus pitch was reassessed during a control visit, usually the observed value of F t was not exactly the same as the one measured in the previous visit. Therefore, the following compromise criterion was adopted: A new, updated WWN acoustic sequence was constructed only when the re-measured value of F t fell outside the noise window previously determined. The temporal variation of tinnitus loudness in the three groups of patients was examined by computing the values of Δ dB t using the patient's values of dB t measured during subsequent control visits. Table 1 summarizes the characteristics of patients of each treatment group together with the clinical measurements of their tinnitus at their first visit. The average time elapsed from the beginning of the acoustic therapy and the last tinnitus measurement was similar in the three groups of patients: 148 dd (+ 20), 145 dd (+ 25), and 127 dd (+ 16), respectively, for the WN, Wa, and WWN groups. Figure 4 shows the variation of tinnitus loudness with time elapsed from the start of therapy for three patients taken as an example (one for each type of therapy) and for one subject initially receiving the Wa therapy and later re-treated with the WWN therapy (see further discussion later).
The mean decibel attenuation between 3 and 6 months of therapy was less than 1 dB in patients of the Wa group and 4-5 dB in those in the WN and WWN groups. In the four patients re-treated with the WWN therapy, the value of dBt measured at the last control visit was compared to that measured at the control visit preceding the change of therapy.
Our method for the treatment of subjective tinnitus differs substantially from previous methods (but see Goldstein et el. Indeed, the most striking result of our study was the marked decrease of tinnitus loudness observed in patients after approximately 4-5 months of daily listening to the WWN sound stimulation but not seen in those listening to either the WN or the Wa sound stimulations for an equivalent amount of time.
The presence of subjects without residual tinnitus in the WWN group but not in the two control groups further strengthens this conclusion. Apart from the beneficial effects on tinnitus loudness perception, another remarkable aspect of this study was the development of a novel tinnitus pitch-matching procedure using binary comparison of tones selected by the patient in a previous test on the basis of their resemblance to tinnitus.
A potential methodological criticism that should be addressed in this study is the lack of control by experimenters over the patients' motivation or willingness to carefully follow the procedures established by the therapeutic listening program.
First, both the Wa and WN therapies were equally ineffective in reducing tinnitus loudness, despite the greater tolerability and pleasantness of the first therapy according to the patients' judgment. The key element of the WST was the auditory stimulation of tinnitus sufferers with masking noise presumably not comprising the tinnitus frequencies, often suggested to be responsible for the exacerbation of the symptom. An alternative explanation for the decreased tinnitus loudness in patients treated with WST might involve a change in the neural reorganization in the tinnitus region induced by stimulation with noise around, but not inside, the tinnitus pitch region.
The aim of our study was to outline the prevalence of hyperlipidemia in patients who had high-frequency hearing loss and tinnitus due to noise exposure. Cochlear hair cells and neural and central auditory pathways are involved in the generation of subjective tinnitus [1]. Decrease in internal diameter of the vascular bed resulting from hyperlipidemia compromises the oxygen transportation capability of the blood to the cochlea, and chronic hypoxia is likely to occur by the reduction in oxygen supply of the inner ear, which in turn would lead to insufficient adjustment of the cochlear metabolism. This may result in the overproduction and accumulation of free radicals, which disturb the microcirculation of the cochlea and play an important role in ischemiainduced cochlear injury [7]. The reasons for the susceptibility to noise-induced hearing loss of patients who have been exposed to a noisy environment have been the subject of various studies. Previous data indicate that the cochlea and the central auditory system age faster and earlier in patients with hyperlipidemia and that the risk of noise-induced hearing loss is much higher [5,11]. The aim of this study was to outline the prevalence of hyperlipidemia in patients who had high-frequency hearing loss and tinnitus due to chronic noise exposure and to evaluate the risk of developing sensory hearing loss in those patients as compared to risk in control subjects.
We conducted this prospective study in 120 consecutive patients with complaints of chronic subjective tinnitus of varying degrees of severity and hearing loss due to noise exposure.
The patients were examined otoscopically and were reviewed by an audiometric test battery including puretone audiometer (AC-30, IAC, Copenhagen, Denmark), stapes reflex, and tympanometry (Amplaid 775, Milan, Italy). Antilipid treatment with statin derivatives was planned once-daily oral dosing for up to 1-2 years (minimum, 12.4 months). We then compared tinnitus scores and hearing levels in patients with no response to antihyperlipidemic therapy and in patients who had a normal blood cholesterol level after the treatment. The duration of tinnitus in patients with noise exposure varied from 2 months to 12 years (mean, 5.5 years). Of 22 patients in the unresponsive group, 6 had high cholesterol and triglyceride, 9 had high triglyceride, and 7 had high cholesterol only before the antilipidemic therapy.
Of 20 patients in the responsive group, 7 had high cholesterol or triglyceride, 10 had high triglyceride, and 3 had high cholesterol only before the antilipidemic therapy.
The difference between the pitch-match frequencies before and after therapy was not significant.
Epidemiological investigations emphasizing the relationship between hearing loss and the risk factors for coronary artery disease date back to the 1960s [18].
Spencer [19] found that 42.3% of 300 patients with different symptoms of inner-ear pathology had clearly defined hyperlipoproteinemia.
The effect of hyperlipidemia on auditory perception has been studied clinically and experimentally. The exact pathological mechanism for the hyperlipidemia-induced hearing loss remains obscure.
In his study of 64 rats, Pillsbury [37] exposed half to loud noise and fed half of each subgroup a fat diet and found elevated auditory brainstem response thresholds in the hyperlipidemic animals. Studies investigating the restorative possibility of a low-cholesterol diet and antihyperlipidemic therapy on hearing loss and tinnitus are very few. LDL apheresis has been reported to be much more effective as compared with standard prednisolone, dextran, and pentoxifylline therapy in patients with sudden hearing loss [9].
In our study, changes in tinnitus scores before and after therapy in the responsive group were significant as compared with those in the unresponsive group.
Tinnitus and hearing loss are frequently encountered after an acute acoustic and blast trauma or chronic noise exposure.
How to cite this article Cevette MJ, Barrs DM, Patel A, Conroy KP, Sydlowski S, Nelson BNNGA, Stepanek J, et al. Background: Recent studies in noise-induced and idiopathic sensorineural hearing loss have suggested that magnesium supplementation may lessen both hearing loss and the severity of tinnitus in patients. Descriptions of tinnitus date back to the time of ancient Egypt, yet science has failed to unravel the mysterious underlying mechanisms that produce these subjective auditory perceptions of sound. Despite these encouraging findings, no controlled study has examined the effect of magnesium supplementation for patients with moderate to severe tinnitus.
Between March 6 and December 10, 2008, patients aged 18 years or older who were seen for an audiological evaluation at Mayo Clinic in Scottsdale, Arizona, and who had a Tinnitus Distress Rating (TDR) scale score from 3 through 8 (Figure 1) were eligible for the study. Participants were given a daily magnesium supplement, 532 mg (Mg Plus Protein, 133-mg tablets; Miller Pharmacal Group, Carol Stream, Illinois). The primary outcome measures were comparisons of TDR scale scores and THI scores as converted to TSS grades at baseline and the end of the study.
The present study indicated that subjects showed significant improvement in their self-rating of tinnitus with a magnesium supplement of 532 mg daily for 3 months.
From 2001 to 2006, we performed a retrospective study of patients suffering from chronic unilateral or bilateral tinnitus that was previously ineffectively treated by oral drugs [betahistine (Betaserc), extract of Ginkgo biloba (EGb 761), tanakan (Tebokan), and cinnarizinedimenhydrinate (Arlevert), singly or in combination]. Tinnitus is the phantom perception of sound in the absence of overt acoustic stimulation [1].
We randomly divided the patients into seven distinct treatment groups and administered treatment as specified.
The pentoxifylline (PTX) group received daily for 10 days an intravenous infusion of 100 mg pentoxifylline and 250 ml physiological saline. In addition, there were groups treated by pentoxifylline plus physiotherapy (PTX-RHB) and pentoxifylline plus physiotherapy and soft laser (PTX-RHB-soft laser), which consisted of a total of 9 persons. The visual analog scale from 0 (no tinnitus) to 10 (unbearable tinnitus) was used for daily evaluation. We used an enhanced method for construction of a binary classification tree-a regression method computed by condition of maximized homogeneity of treatment methods used [by Agapurin (Trental), Cavinton, lidocaine] in terminal leaves. In computing progress, we found that treatment PTX and age metric were ambiguous and so we dropped them, with no effect on our results. Combination of Cavinton and physiotherapy was the most effective treatment seen in all the groups (see Fig. The groups treated by pentoxifylline plus physiotherapy (PTX-RHB) and pentoxifylline plus physiotherapy and soft laser (PTX-RHB-soft laser) consisted of a total of 9 persons, and the outcomes were considered to be statistically insignificant. Because tinnitus is a subjective symptom, we used the subjective scale-the visual analog scale-as the only parameter. We summarize our long-tean clinical experiences with an inner-ear drug delivery system (DDS) for control of tinnitus.
The dangers of perforating the eardrum and of inciting the discomfort of vertigo as a result of the transtympanic injection of dexamethasone are minimal.
The management of tinnitus has been the topic of many articles and special meetings of scientific societies. Our clinical trials of an inner-ear drug delivery system (DDS) for control of inner-ear problems began in 1974 [1]. Consequently, in 1981, we began to use liquid dexamethasone for STT to the inner ear, to control various kinds of inner-ear diseases and symptoms [3].
The procedure we employed for our therapeutic modality has already been reported elsewhere [4-7]. To evaluate the control effects of this therapy on tinnitus, a 10-division subjective evaluation system was used. Short-term effects on tinnitus were evaluated 2 weeks after the fourth intratympanic dexamethasone perfusion.
The short-term overall effects on tinnitus of dexamethasone perfusion into the tympanic cavity were positive in 75% of patients. Figure 2 depicts the effectiveness of drug management of tinnitus in the presence of various underlying diseases. The effects of our DDS trials on tinnitus control and average hearing levels ranged between 64% and 72%.
Evaluation of the effects on various pitches of tinnitus indicates that high-tone tinnitus was less improved than was low-pitched tinnitus. The long-term effects on tinnitus of dexamethasone perfusion into the tympanic cavity were evaluated at approximately 6 months after the last injection. In this intratympanic dexamethasone perfusion technique, it is assumed that the medicine that was introduced directly into the tympanic cavity acts on the plexus tympanicus, is absorbed through the round window, and acts on the inner ear [8-13] . The short-term side effects of the inner-ear DDS that we describe include pain at the time of tympanic puncture and temporary vertigo immediately after the injection. Tinnitus continues to be a significant and costly health problem without a uniformly accepted treatment. It is reported to occur in up to 30% of individuals in those nations, with 10-15% of individuals experiencing symptoms significant enough to require medical attention [1]. Currently, no drug exists with an indication for tinnitus, though several are used "off-label," and side effects can be an issue that limits compliance. We excluded studies not focused on tinnitus, nonpharmacological articles, and studies addressing a particular neurootological disease. Heller [1] reviewed classification systems of tinnitus, although none are universally used.
Although the anticholinergic, antihistaminic, and adrenergic activities of tricyclic antidepressants are postulated to play a role in the mitigation of tinnitus [9], no basic science studies have demonstrated a plausible biological mechanism.
In a small study, trimipramine failed to demonstrate any subjective or audiometric benefit over placebo [9]. Decreased GABA activity is postulated as a potential causative factor for tinnitus that results from abnormal activation of central nervous system auditory pathways.
Alprazolam, a drug that potentiates GABA activity at GABA-A receptors, was found to decrease both subjective loudness and intensity matching of tinnitus in a double-blind, placebo-controlled, prospective study [18].
Subjective outcomes measures ranged from yes or no responses on tinnitus improvement, to visual analog scales, to the 25- question THI.
In guinea pigs, a model of prostaglandin activity suggested that prostaglandins may act as neuromodulators of cochlear afferent transmission [22]. The first demonstrated a subjective report of 33% response to active treatment as compared to 0% with placebo treatment and showed that responders to medication had statistically significantly decreased subjective rating-scale scores of tinnitus after 16 days of treatment, as compared to the scores of nonresponders [23].
Subjective outcome measures were limited to yes or no improvement replies and visual analog scales, without any tools to measure impact of tinnitus on functioning.
In a double-blind, placebo-controlled, prospective trial of 48 patients treated with nicotinamide (vitamin B3), results were no better than those from placebo [29]. The reported incidence of zinc deficiency in patients with tinnitus is inconsistent, with some reporting a positive correlation [31-35] and others finding no relationship [36,37].
All studies used an analog subjective tinnitus rating scale-either from 0 to 7 or from 0 to 10-as the main outcome measure, with one trial [35] using loudness matching as an additional outcome measure.
Improvement in blood circulation to the organ of Corti has been suggested as a mechanism for ameliorating tinnitus [38]. One trial demonstrated a statistically significant decrease in tinnitus loudness matching as compared with results from placebo [40]. Only those who reported some improvement (n = 21) were invited into a randomized, placebo-controlled, crossover study. Similarly, despite their widespread use and in the absence of compelling clinical evidence, none of the commonly advocated nutritional supplements are any more effective than is placebo in tinnitus control. In particular, several animal studies suggested that changes in the GABA-A-receptor binding in the brainstem and inferior colliculus may be responsible for tinnitus, though the relationships are complex.
The zinc studies have similar characteristics, although a trend toward helping elderly patients with zinc deficiency was identified [36]. Given the lack of adequate basic science models, disparity in symptom definitions and outcome measures, and overall lack of power of past studies, it is also not possible to exclude most (if not all) of the reviewed treatments from future analysis.
Such models as conditioned lick suppression in the presence of sound [46] still rely on salicylate toxicity that may not accurately mimic the wide range of potential causes of tinnitus. Studies should include a table that offers information on age, gender, subjective versus objective tinnitus, laterality, constant versus intermittent, location (central versus cochlear), duration, hearing function, any known tinnitus causing disease, psychiatric illness, systemic illness, current medications for tinnitus, past medications for tinnitus, and baseline measures of the impact of tinnitus on quality of life.
However, every effort should be made to use subjective measures that have clinical significance, with an a priori decision on the defined level of improvement that constitutes a relevant outcome. Studies should be prospective, randomized, doubleblind, placebo-controlled, crossover investigations with adequate washout time between placebo and active treatment. DUDLEY JOHNSTON WEIDER, 66, died suddenly on Friday, February 18, 2005, while skiing into the Dartmouth Grant. He graduated from Bay Village High School in Ohio, where he was a member of the undefeated football team and competed in speed skating. Luke's Hospital in Cleveland, he was a staff physician and then a service unit director at the U.S. He was a member of the Dartmouth Medical School faculty, becoming professor of surgery in 1989. Whether he was easing the fears of young children by wearing bear claw slippers into surgery or meeting patients in need at all hours of the day or night, he consistently shared his warmth and concern for all who came under his care. He was secretary of the New Hampshire Medical Society from 1984 to 1988, vice president in 1989, president in 1990, and a trustee from 1988 to the present. The activities he enjoyed included alpine, telemark, and Nordic skiing, snowshoeing, hiking, mountain climbing, fishing, speed skating, in-line skating, biking, and running.
In 1988, he received honorable mention for the Denali Pro Mountaineer of the Year outdoor ethics award from ENN Daily News for rendering medical services at the ranger camp at 14,200 feet on Mount McKinley. He repeated the trip when his son, David, was in high school and when his daughter Heidi was in middle school.
Dudley, in his very quiet, reserved, and New England master-of-understatement ways, was very impressive in so many areas of his life, family, and work and in his incredible dedication to his patients and their health and wellbeing.
I think his openness and ability to interact informally on clinical and basic science areas were two of the aspects that made him such a strong supporter of the PMS. He and Joan attended all the PMS winter ski meetings in Aspen and also all the meetings of the International Symposium on Inner Ear Medicine and Surgery in Snowmass, Colorado. He would have been very proud of the accomplishments that he was instrumental in bringing to fruition.
He was the best and will be greatly missed by all his friends, colleagues, and patients and by his wonderful family. He liked a paper on fistula testing that I had presented and invited me to come up to Dartmouth and participate in a course that he was sponsoring.
He was also an amazing athlete, climbing mountains, performing marathons and cross-country skiing across vast spaces. When I informed Ron Steenerson of Dudley's untimely death, Ron told me, "Dudley was a good friend!" I replied that lots of people would say that. He did not hesitate to share his knowledge with his colleagues, always giving them good advice, encouragement, and support in their endeavors. Dudley infused his medical practice with the same zeal and enthusiasm that he had for life. He and I were contemporaries, and I could not even imagine doing the things that he accomplished athletically.
DUDLEY WEIDER passed away this year while engaged in one of his favorite past-times: cross-country skiing. We often sought each other's counsel on a difficult case, talking on the telephone into the night, which was three hours later for him than for me. When one sought Dud's help on a personal matter, he did not hesitate to throw everything aside and come to our aid.
They suffered recurrent perilymphatic fistula, and Dudley was seeking answers beyond the normal realms of our understanding.
It is all too easy to hear only one's own thoughts; however, to be at one with his surroundings and to listen to his patients were Dudley's key to inspiration. Dudley and I usually jogged together, at which times he would regale me with his latest adventure. Often, we find multisensory syndromes combined with tinnitus, hearing impairment, vertigo, and nausea. Low-tone tinnitus is more frequently found in Meniere's disease and some other cochleo-apical disorders.
In the high-tone range, most frequently tinnitus is matched and related to such conditions as noise trauma, whiplash, head and skull trauma, cardiovascular failures, stress, and toxic events, including pharmaceutical use, nicotine or drug abuse, and acoustic neuromas. Owing to the size of the workload, we limited ours efforts to constructing a sample from those 757 patients randomly selected from a major group of neurootological patients (we process more than 10,000 files of neurootological patients, many of whom suffer from one or another type of tinnitus). We then conducted objective and quantitative electrophysiological measurements of the acoustic pathways via otoacoustic emissions, acoustic brainstem-evoked potentials, and acoustic late or cortical evoked potentials.
We performed vestibulospinal recording of the CCG with the Romberg standing test and the Unterberger-Fukuda stepping test using USCCG and the human space trail. However, for this study, we present the broad spectrum of subjective complaints as reported by the patients with a broad variety of findings. This is shown for instance, in Figures 6 and 7, wherein the typical tinnitus phenomena are matched on different hearing zones in the audiograms of the right and left sides. Therefore, we prepared a specific, detailed analysis of the background of head and neck trauma (Fig.
Our search presented us with a great amount of data (more than 500 parameters per case), which we transferred into a digital version of the databank to preserve the anonymity of this sample of patients.
The other identification indicators (weight, height, body mass index, and average systolic and diastolic blood pressure) lie within the expected range of this sample taken for Germany. For vegetative symptoms, such as the occurrence of nausea in perhaps one of four patients, see Figure 9. Acoustic, vestibular, and behavioral and psychosomatic symptoms are intertwined and seemingly interact with one another. In a subsequent publication, we will deal with the outcome of the objective and quantitative measurements in audiology, equilibriometry, and the like in our group of 757 cases of endogenous tinnitus. Therefore, speech discrimination tests with a competing noise are used to establish the pathological camouflaging effects in the individual patient. According to our experience, ascending degeneration can be established best by a supplementary distorted- speech test. According to current knowledge, five separate morphologicallevels of speech perception are distinguished. Level 3 represents the cochlea, including the cochlear amplifier and afferent transmission, and cochlear analyzing functions. The findings call for new proposals for precise assessment of specific hearing capacity, previously called selection ability.
The inner hair cells, therefore, are considered the true sensory cells of the auditory system. Ascending degeneration and its direct effect on speech discrimination become apparent in the slowly developing cocktail-party effect. As a consequence, the author recommended measuring exclusively the distortion product OAEs when assessing noise-induced hearing loss. For our experiments, we chose the distorted-speech method because not only does it measure the speech signal-masking effect (which is of great importance for detecting such damage) but very often it discloses, in the presence of an ascending degeneration, a marked impairment in the time-related analysis of an acoustic signal [11].
As depicted in Figure 1, sound processing is not performed by the inner ear alone but includes several levels of the auditory system. Referring to Schubert's tests, we at first installed-5,-10, and-15 dB as reverberation grades and a reverberation time of 5 seconds but, when put into practice, the findings at the reverberation grade of -15 dB proved to be the most useful.
Discrimination curves in age groups 1-7 for (A) nondistorted monosyllables and (B) distorted monosyllables at reverberation grade -15 dB (Freiburg Hahlbrock Word Test) .
The word discrimination capacity is derived from the respective discrimination scores for nondistorted and distorted monosyllables at levels of 50, 70, and 90 dB, and the reverberation ratio then is calculated as demonstrated in Figure 3.
Measurement results of reverberation ratios for hearing, conductive hearing loss, combined hearing loss, and sensorineural hearing loss. Therefore, an inclusion of the distortedspeech test into the audiometric test battery seems essential. Dissimilar reverberation ratios (R) at approximately symmetrical pure-tone hearing loss in a work noise-exposed laborer. In addition, with this subjective hearing test method, the plasticity of the central auditory system may be recorded or assumed. The constantly improving topodiagnostic possibilities compel us now to consider five levels of sound perception and processing as basic components of our audiometric test battery and to draw audiological evaluations from diverse, meticulously designed test methods.
In an audiometric test battery, the distorted-speech test (like any other measuring method) is especially indispensable in localizing distinct damage levels in the auditory system.
However, when damage to the outer hair cell layer must be identified, measurement of the OAEs is the first choice [9,19,20]. Pathological reverberation ratios instantly tell the examiner that specified tests might be necessary in one case or another. 10, formerly distributed by Westra Electronic GmbH, Wertingen and, at present, by their successor Heike Kammermeier, Bergstrasse 16, 89438 Holzheim-Eppisburg, Germany. The Windowed Sound Therapy: A New Empirical Approach for an Effective Personalized Treatment of Tinnitus.
We assessed the long-term effects on tinnitus perception in patients listening to notched noise stimuli (referred to as windowed sound therapy [WST]) by measuring the variation of subjects' tinnitus loudness over a period of 2-12 months.
Epidemiological surveys indicate that the sensation caused by the tinnitus is present in 5-15% of the human population. All subjects of the study were patients reporting a ringing or hissing sound in one or both ears (Table 1) and willing to take part voluntarily in the experiment and to scrupulously follow the assigned therapy. With a few exceptions, we noted that all patients had, in one or both ears, a more or less pronounced hearing loss at frequencies above 3-4 kHz, an important predisposing factor for the occurrence of tinnitus [9]. We stopped the procedure when a patient reported that the pitch of the comparison stimulus was similar to the tinnitus pitch. The difference between the two measurements was the estimated loudness of the patient's tinnitus (dB t [decibels SL]). Pure tones were generated with a function generator (Kenwood model FG-273; Kenwood Corporation, Taiwan) connected to a custom portable electronic switchboard (left, right, binaural), and the output signal was sent to a pair of Sennheiser HD 202 (Sennheiser Sales, Dublin, Ireland) closed-cup headphones.
Pure tones are commonly used for measuring the pitch of both noise-like and tonal tinnitus [10]. In such cases, the frequency value of the matching tone was noted, and the tone sweep was resumed, starting from the frequency at which it had been interrupted.
We asked subjects which of the previously identified tones were more similar to the pitch of their tinnitus. This could happen for several reasons: presence of different kinds of tinnitus, such as a ringing associated to hissing tinnitus, presence of multiple tinnitus spectral peaks [13], or octave confusion. WWN was constructed from a 10-minute sequence of white noise generated by the white noise generation function of a suitable software for sound analysis (AVISOFT; Avisoft Bioacoustics, Berlin, Germany).
For these reasons, the width of the erased band of WWN was set prudently to a value double the width of the critical band of the tinnitus frequency. Spectral characterization of the three sound therapies with decibel values in relative units. This was expected, as any procedure of pitch assessment is inherently imprecise for reasons already discussed. In this case, the patient was asked to return the old disk and listen to a new disk that contained the usual 8-minute sequence of equalized broadband noise recorded after a notch centered at the new tinnitus frequency or frequencies was created following the method explained earlier. Conversely, the presence of two control treatments allowed the effectiveness of the WWN therapy to be established regardless of the type of comparison stimuli used for the measurement of tinnitus loudness. The number of control visits (and re-measurements of dB t ) varied from one to seven per patient. When subsequent visits of the patient fell within the same temporal class, only the value of dBt measured during the last visit within the class was considered for analysis. If the difference among means was statistically significant, we used the multiple-comparisons procedure of the Kruskal- Wallis test to test the difference of mean value between pairs of treatments. Patients of the three groups did not differ significantly regarding gender ratio, mean age, mean hearing loss, and mean value of tinnitus parameters.


In the WWN-treated patient, tinnitus intensity decreased by 12 dB after only 1 month of therapy and by 15 dB at the end of the observation period (after 7 months).
Variation of tinnitus loudness over time in four patients (indicated with a different symbol) taken as an example. The mean attenuation between 7 and 12 months was less than 1 dB in patients of both the WN and Wa groups and 3 dB in those of the WWN group. Results showed a remarkable reduction of tinnitus loudness in the three patients who were initially given the Wa therapy (one of them recovered from tinnitus; see Fig.
Furthermore, about two-thirds of the differences were below 1 kHz, and approximately one-half of the differences were below 0.6 kHz. These acoustic stimulations are standard for each subject; they are not personalized in relation to the tinnitus frequency that characterizes the subjective tinnitus. Furthermore, patient's estimation of tinnitus loudness showed a clear negative relationship with the time of WST application; loudness decreased by approximately 1 dB per month of application of the therapy (see Fig. This procedure yielded pitch estimates characterized by low between-session variability (mean absolute difference of 1.1 kHz between the tinnitus pitch measured at the initial visit and at the first control visit after 1-2 months). This could weaken the conclusions of our study if the patient's "at-home" listening behavior had been affected by the type of acoustic therapy they received. Second, tinnitus loudness did not decrease significantly with months of application of the sound therapy by patients of the two control groups.
This discrepancy, however, may be easily explained by considering the rough clinical procedure used in our study for finding pitch matches suitable for the loudnessmatching test. In our study, the pitchmatching test conducted during audiological evaluation was aimed solely at obtaining a matching tone only approximately resembling the tinnitus frequency, the tinnitus pitch being accurately measured in a separate experimental test (see under Methods). Jastreboff and Jastreboff [21] stressed the importance of ensuring that the sound-enriched environment provided with the TRT should not contain sounds causing annoyance and exacerbation of the tinnitus sensation. The auditory stimulation of patients with waterfall noise recorded underwater (Wa therapy) did not contain significant energy in the frequency range above 3-4 kHz (where hearing loss usually occurs and most tinnitus sensations pitch) and, furthermore, appeared to be better tolerated as compared to the stimulation with white noise (WN sound therapy).
For instance, it has been hypothesized the overrepresentation of the edge frequencies before the hearing loss region is responsible for the tinnitus sensation [1].
Low-Cholesterol Diet and Antilipid Therapy in Managing Tinnitus and Hearing Loss in Patients with Noise-Induced Hearing Loss and Hyperlipidemia.
We investigated the role of a low-cholesterol diet and antihyperlipidemic therapy to alleviate the severity of tinnitus and possibly promote hearing gain after therapy in patients with acoustic trauma. Analysis of the epidemiological data indicates that exposure to noise is widespread and is one of the most common causes of tinnitus, which leads to various somatic and psychological disorders and interferes with the quality of life [2]. Auditory perception in such cochleas is very sensitive to reduction of the oxygenation in the inner ear [6]. Platelet aggregation and blood viscosity due to high lipid levels will intensify inner-ear damage owing to slowing of microcirculation and will contribute to the development of both progressive and sudden hearing loss [8,9]. Gratton and Wright [10] demonstrated the accumulation of lipid in the stria vascularis and outer hair cells in chinchillas after experimentally induced hypercholesterolemia, which might intensify the detrimental effect of ototoxic drugs or noise. We instituted a low-cholesterol diet and antihyperlipidemic therapy to investigate whether any benefit accrued in terms of hearing gain and tinnitus relief. The project was approved by the local medical research ethical committee, and we obtained informed consent from each patient.
Audiometric tests included air- and boneconduction thresholds for pure tones of 125-8,000 Hz, tests of speech reception and speech discrimination, contralateral and ipsilateral reflex measurements, and tympanometry. Measurement of loudness of the tinnitus was based on subjective assessment by the patients.
Daily dosage ranged from 10 to 40 mg for simvastatin (Zocor) and from 10 to 80 mg for atorvastatin calcium (Lipitor).
Average ages of patients in the unresponsive and the responsive groups were 39 and 42 years, respectively. Wilcoxon and Mann-Whitney U tests were used to compare the pretreatment data with the posttreatment results and to compare the results of responders and nonresponders. None of these patients demonstrated any drop to normal ranges in cholesterol or triglyceride values after the treatment.
When those patients were asked to qualify the severity of their tinnitus, seven rated their tinnitus as the same (35%), two rated it as increased (10%), seven rated it as decreased (35%), and four had no tinnitus (20%). The correlation between serum lipids and auditory dysfunction has been investigated before, and it has been reported that sensorineural hearing loss is more prominent in those with high levels of cholesterol, triglyceride, and lowLDL and in patients with low HDL concentration [18-23]. Increased blood viscosity and atherosclerosis of the cochlear vessels reduce the blood perfusion of the cochlea and promote hearing impairment [6,8,19,20,23,24]. When patients were required to qualify the severity of their tinnitus, 35% of the patients in the responsive group rated their tinnitus as decreased, and 20% of patients reported no tinnitus. Even though other factors making the patients susceptible to noise-induced hearing loss should be considered, on the basis of present results it can be concluded that the incidence of hyperlipidemia is high among patients with noise-induced hearing loss and that significant improvement in lowered intensity of tinnitus and in average hearing thresholds at higher frequencies can be achieved after lowering patients' serum lipid level [43].
Further epidemiological evidence indicates that all age groups of Americans fall short of the recommended daily allowance for magnesium by 100 mg daily. These perceptions may be manifestations of damage resulting from noise exposure, ototoxicity, or other abnormal conditions of the auditory system.
Additionally, no study to date has examined self-reported tinnitus severity before and after magnesium supplementation. The TDR was adapted from an existing pain scale, with the subject rating him- or herself between 0 (no tinnitus) to 10 (worst possible tinnitus). The Tinnitus Handicap Inventory is a 25-item self-report questionnaire that the patient can complete in about 10 minutes. A review by the Division of Cardiovascular Diseases indicated that daily magnesium supplementation at the level of 532 mg was benign for heart patients whose kidney function was normal. After beginning magnesium supplementation, the participants rated themselves daily for 3 months using the TDR. The data collected for each participant included informed consent, sex, date of birth, hearing threshold at 8 frequencies (250, 500, 1,000, 2,000, 3,000, 4,000, 6,000, and 8,000 Hz), weekly diaries of daily TDR ratings of tinnitus, THI questionnaires at baseline and the end of the study, dates of first and last dose of magnesium, number of tablets used, reason for discontinuation, and adverse events. Of these, 2 patients (8%) discontinued the study because of adverse events and subsequently had no follow-up data. Change in tinnitus rating in 26 patients from baseline to 3 months after treatment with magnesium.
In fact, significant improvement in the TDR occurred as early as 1 month into the study, suggesting that benefit of magnesium supplementation occurred early in treatment and was sustained throughout the 3 months of the study. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. PhD, Department of Otolaryngology, Section of Audiology - Mayo Clinic - Scottsdale - AC - United States. MD, Department of Otolaryngology, Head and Neck Surgery - Mayo Clinic - Scottsdale - United States. AuD, Department of Otolaryngology, Section of Audiology - Mayo Clinic - Scottsdale - United States. AuD, Section of Audiology - Cleveland Clinic Head and Neck Institute - Cleveland - United States.
BS, Department of Otolaryngology, Section of Audiology - Mayo Clinic - Scottsdale - United States. MD, Division of Preventive, Occupational and Aerospace Medicine - Mayo Clinic - Scottsdale - United States.
It is well known that chronic tinnitus is difficult to treat, though lots of modalities are used for treatment.
Because the studies available on MEDLINE report different outcomes [8,10-12,14], we tried to evaluate the most widely used therapeutic approaches in our hospital: drop infusion of lidocaine, vinpocetine, or pentoxifylline and combination of these drugs with low-level laser therapy and physiotherapy. Before and after treatment, each patient underwent basic ear, nose, and throat examination, including otomicroscopy, basic vestibular examination, pure-tone audiometry, and tinnitometry. Those in the Cavinton group received daily for 10 days an intravenous infusion of 20 mg Cavinton plus 250 ml physiological saline, and oral Cavinton 2 Χ 10 mg (0-2-2). As the outcomes were considered to be statistically insignificant, the findings from these groups are not evaluated further. Patients' symptoms were evaluated as improved if their tinnitus was perceived to be better by two or more points on this scale.
We had four metrics-age, duration of tinnitus, gender, and audiometry-each of which could be used to divide cases into branches. The boundary in the age metric was found at 62 years; in tinnitus duration, the value was 15 months. Effectiveness of therapy in each of seven treatment groups, determined by using a visual analog scale. Only 1 patient of those 9 experienced a decrease in tinnitus intensity; the rest saw no change. The most effective treatment according to the age, tinnitus duration, and audiometric findings.
Many patients with positive tinnitus changes (according to the visual analog scale) experienced changes in quality of life, so the quality-of-life questionnaire should be used in further studies. The inner-ear DDS consist of transtympanic perfusion of 2 or 4 mg dexamethasone to the round window via the middle ear. We believe that the transtympanic infusion technique is an effective DDS for control of inner-ear diseases and symptoms. In this article, we describe some 15 years of clinical experience with steroid targeting therapy (STT) to the inner ear for control of tinnitus. The inner-ear DDS that we employ consists of transtympanic perfusion of medicine to the round window via the middle ear. The intratympanic injection was performed in our outpatient clinic with the patient in the sitting or the supine position. The subjects were 3,978 ears of 3,041 patients who received intratympanic dexamethasone perfusion for the management of vertigo, tinnitus, and the like.
Patients then were investigated 6 months after the injection, at which time the long-term effects on tinnitus were evaluated. Effects on tinnitus of intratympanic dexamethasone perfusion in the presence of various underlying diseases. Effects on tinnitus of intratympanic dexamethasone perfusion in relation to disease duration. The same 10-division subjective evaluation was used as was applied for the short-term evaluation. The mechanism of action of this therapeutic modality is multifactorial, including sedative effects, a metabolic improving effect, and an edema-relieving effect, which may eliminate abnormal excitation of auditory hair cells, which are believed to cause tinnitus.
Itoh A, Sakata E: Treatment of vestibular disorderIntratympanic dexamethasone injection and inner ear anesthesia with lidocaine.
Ristow W: Zur Behandlung der Meniereschen Krankheit mittels tympanaler Labyrinthanaesthesie. A wide variety of studies exploring prescription, supplement, and vitamin therapies are assessed for efficacy of treatment and for establishing consistencies in symptom definition, assessment, and outcome measures. Of the 342,903 US veterans receiving disability pensions in 2004, 84% received payment for a tinnitus disability.
In addition, its presence in isolation or in the setting of specific disease entities, such as hearing loss, Meniere's disease, or trauma, is inconsistent. As a result, despite their efficacy, widespread use for such a common problem is unlikely and economically unfeasible. Since then, Dobie [6] reviewed well-controlled, randomized clinical trials for all treatments of tinnitus. In comparison, multiple nutritional supplements are sold individually or in combination with claims of tinnitus relief.
Of the 59 results remaining, primary focus was given to summarizing developments since previous reviews [5-7]. Therefore, we reviewed studies in our effort for their inclusion of the symptom location, character, loudness, pitch, impact on daily life, association with hearing loss or other neurootological disease, and verification with such measures as audiometry, pitch matching, loudness matching, and masking level.
A trial of nortriptyline demonstrated statistically significant subjective and objective improvements within both treatment and placebo groups but essentially no differences between groups [10].
The inferior colliculus projects auditory information via the ventral medial geniculate body of the thalamus in the classic auditory pathway.
No statistical comparison was made between treatment and placebo groups, only within those groups.
The Lioresal trial used loudness matching, pitch matching, and maskability as audiometric outcomes.
Audiometric outcomes in the most recent trials included tinnitus frequency and intensity matching. More recently, the anticoagulant sodium enoxaparin was compared to combination therapy of corticosteroids, vasoactive agents, multivitamins, and anticoagulants, with a reported abatement of tinnitus symptoms [27]. A statistically significant increased incidence of vitamin B 12 deficiency was identified in patients with chronic tinnitus and noise-induced hearing loss (NIHL) as compared with NIHL and normal subjects, with reported improved symptoms after replacement therapy [30]. No substantial basic science evidence demonstrates the role of zinc in the pathogenesis or treatment of tinnitus.
The first reported no significant difference between Zn2+ , 22 mg three times daily, and placebo [37]. No discussion of statistical power was mentioned in any study, and enrollment ranged from 40 to 96 subjects. The statistical significance was recorded as p Ginkgo biloba treatment before being randomly assigned to oral therapy versus placebo. Even with this selection, no significant improvement on subjective scores of tinnitus was found as compared to results from placebo.
The THI was used as a quality-of-life outcome in the most recent study [42], and a similar questionnaire was used in the largest study [41]. Despite this lack of conclusive evidence, much can be gathered from the available research on the pharmacological management of tinnitus. Other antidepressants, such as SSRIs, likely are similarly effective, although a placebocontrolled, prospective study of SSRI medications is needed. The available clinical studies using benzodiazepines are of short duration and have limited patient numbers.
Thus, though zinc deficiency can be a cause of tinnitus, zinc replacement in tinnitus sufferers with normal zinc levels is of little benefit.
Clinical investigations, including a large number of subjects as well as meta-analysis, failed to show any benefit over placebo. Given that a placebo can result in a 30-40% response rate for tinnitus, similar findings with treatment should be presented with caution [10,48]. Antidepressant treatment of tinnitus patients: Report of a randomized clinical trial and clinical prediction of benefit.
GABAAbenzodiazepine- chloride receptor-targeted therapy for tinnitus control: Preliminary report. Effectiveness of Ginkgo biloba in treating tinnitus: Double blind, placebo controlled trial. Ginkgo biloba does not benefit patients with tinnitus: A randomized placebo-controlled double-blind trial and meta-analysis of randomized trials. Enhancing intrinsic cochlear stress defenses to reduce noise-induced hearing loss [candidate's thesis].
His contributions to otology, neurootology, and tinnitology have been significant and have enhanced our understanding of tinnitus for the benefit of tinnitus patients. He received an undergraduate degree in 1960 from Dartmouth College, where he was a member of Delta Upsilon fraternity and joined Church of Christ his freshman year. Centurion Club - Deafness Research Foundation, the Reserve Commission Officers Association of the U.S.
He was president of the New Hampshire Society of Otolaryngology and Maxillo-Facial Surgery in 1983. Weider was a deeply spiritual man, and his involvement in the church was an important and fulfilling part of his life.
He competed in numerous marathons, including the Burlington, Keene, Boston, and Marine Corps marathons and the first marathon held in Antarctica. He and his son rode through England and Scotland, meeting up periodically with his wife and daughters. He loved being able to see different cultures, meet and learn about new people, and try different things, including bungee jumping in New Zealand at age 60.
After a wonderful dinner, he spent three straight hours talking to several patients and trying to help them to cope with their intractable dizziness.
He always called his colleagues and the experts to try to ensure that he had analyzed the clinical and personalemotional problem and looked at all the possibilities. He served on the program committee and the awards selection committee and was actively involved in all aspects of making the PMS a great success. I will propose at that meeting that Dudley Weider, MD, be given posthumously the Prosper Meniere's Society Gold Medal Honor Award for all his contributions on all levels to the success of the society and for his dedication to the best possible care of all his patients - particularly, those on whom everyone else had given up.
Our sincere condolences to Joan and the "kids." Words cannot express how important Dudley was to all of us who were fortunate to have had him in our lives.
He worked hard for his patients, yet found time to do clinical research and travel extensively, interacting with others in our field at those times. But it has been a great privilege to know him, a privilege to interact with him professionally, and a privilege to know his family.
His example of living will always be an ideal to those who knew him and to those whom he loved. We extend our sincere condolences to his family and particularly to Joan, who has been not only a tremendously supportive wife but Dudley's closest partner and friend. He was devoted to his wife, family, and friends, and his patients were as important to him as if they were family.
What I would like to address are his more personal qualities, which I had the privilege of learning from close association with Dudley.
Dudley was also most considerate, allowing others to have the favored fishing spot, always thinking of others first. I received this news with shock and disbelief, for I knew him to be a man of tremendous endurance and stamina, who only a few years ago was seeking out such extreme physical pursuits as climbing Mt. The cause of the fistula is often a sudden increase in the intracranial pressure, but why were these individuals prone to recurrence of this condition? I believe that his treatment with ventricular shunts was a brave step and now promises patients release from their disorder. From more than 10,000 cases, we evaluated 757 randomly selected neurootological patients suffering from endogenous tinnitus. However, what could be proved by various authors since 1985 is that endogenous tinnitus is significantly related to dysfunctions in the human temporal lobe (Brodmann area 41). We administered a full spectrum of neurootometric testing to all 757 patients; the investigation protocol for thorough data analysis (more than 500 parameters) included five procedures.
After all the files of the patients were transferred into digital lists and nets of digital data, we could select the various groups of complaints to derive a representative statistic.
The most frequent quality of tinnitus distortion reported was a whizzing sound in either ear or in both (54.02%). Figure 21 demonstrates a specific differentiation with respect to facial nerve paralysis cases.
We easily designated a group of patients who demonstrate a genuine objective sound in the head as experiencing bruits.
In future, this must be taken into consideration in developing a spectrum of therapeutic procedures not only in the field of pharmacotherapy but in psychotherapy and physiotherapy and in applying such physical measures as magnetotherapy. We found diabetes mellitus more frequently in the group with the exogenous or unmaskable tinnitus, whereas hyperlipidemia was reported twice as often in the group with endogenous or maskable tinnitus as in those with the unmaskable type.
On the functional state of central vestibular structures in monaural symptomatic tinnitus patients. About the Strength of the Neck in Linking the Head to the Trunk as Measured by the US-CCG . Interdisciplinary clinical vertigo studies in whiplash lesions to the ligamenta alaria by means of dynamic MRI-findings in combination with ultrasound cranio-corpo-graphy (USCCG). Medical classification of tinnitus between bruits exogenous and endogenous tinnitus and other types of tinnitus. Die Differenzierung zwischen endogenem und exogenem Tinnitus [The differentiation between endogenous and exogenous tinnitus]. However, they have disadvantages as regards the many patients suffering from inner ear hearing impairments in the high-tone frequency range, such as presbyacusia due to advanced age or noiseinduced hearing loss due to work noise, environmental noise, or noises connected with military activities.
As discussions about the most practical method of testing speech discrimination capacity have so far not produced satisfactory solutions, we decided to develop a test that permits us to assess a patient's impaired selective hearing capacity as compared to normal hearing, using an easily performed, quick, and quantitatively reliable test based on tests commonly used in otolaryngologists' offices and by clinical audiologists. They represent principal stages in the hearing and selection capacity of the auditory system (see Fig. Electron-microscopical reproductions of the structures of the cochlea, hearing nerves, and spiral ganglia after long-term dose-controlled noise exposure show the resulting destruction first of the outer, then the inner, hair cells and, eventually, of the corresponding afferent nerve fibers, including the spiral ganglia [5]. Their sensitivity is steered by the active movement of the outer hair cells and olivocochlear efferent nerve fibers.
Quantitative assessment, however, is difficult, especially with regard to comparable data from quantitative audiometric assessment. In animal experiments, he exposed guinea pigs to 10 single-spark impulses with peak values of 164 dB. This condition becomes evident in affected patients who are unable to follow broadcast information in echoing surroundings, such as train stations. Taking into consideration the complicated mechanisms of hearing, Schubert [12] had recommended several rather intricate speech discrimination tests, among them a distorted-speech hearing test that allowed him to classify selection capacity as an inner ear performance. In cases of sensorineural hearing loss, it offers a fast method of verifying a dysfunction of selection capacity, to establish the degree of damage and possibly even the level of origin by evaluating all audiometric test results combined.
The distorted-speech test, when employed in the described way, even permits a quantification to some extent. With damage to the hearing nerve and to superior brain levels, the aggravated-speech testsspeech tests with background noises and distorted speech-are, aside from electric response audiometry, brainstem evoked response audiometry, and magnetic field audiometry, equally useful for diagnostic purposes. Experimentell-mikroskopische Studie zur Frage der Lokalisation von bleibenden Horschaden nach Industrielarmbelastung mit tonalen Gerauschanteilen.
Evidence of mechanical non-linearity and frequency selective wave amplification in the cochlea.
Zur Definition "Selektionsfahigkeit" bei erschwertem Sprachverstehen als Folge peripherer Perzeptionsschaden.
Diskriminationsverhalten von Normal- und Schwerhörigen bei kritischem Signalrauschabstand. Zur Bewertung von Inaktivitatserscheinungen des auditorischen Systems bei Patienten mit einSeltIger Mittelohrschwerhörigkeit vor und nach operativer Therapie. Neuromagnetic localization of the M 100 component in patients with peripheral hearing loss. The effect of impulse noise exposure on distortion product otoacoustic emissions in the awake guinea pig.
We tested the effectiveness of WST using non-notched broadband noise and noise of water as control sound therapies.
Tinnitus is thought to consist of an abnormal neural activity of the auditory pathways [1].
In addition, though Jastreboff and Jastreboff [7] claimed that all types of tinnitus and intolerance to sounds can be beneficially treated with TRT, intolerances toward the wearable acoustic prostheses delivering the masking auditory stimuli (noise generators) have been reported, presumably owing to the annoyance caused by stimulation of the patient with frequencies similar to that of the tinnitus [8]. All participants were provided with informed consent, previously approved by the Ethics Committee of the School of Medicine of the University of Parma, before starting the therapy. Some patients (~25%) experienced difficulty in performing reliable comparisons because of the markedly different perceptual quality of pure tones as compared to that of their tinnitus.
Comparison tones (or NBN segments) were presented consecutively for a few seconds at the interstimulus interval of about 1 second. In a subject reporting the tinnitus only, or predominantly, in one ear, the comparison tone was presented contralaterally, whereas if the intensity of the subject's tinnitus sensation was similar in both ears, the tone to be matched was presented bilaterally.
In our case, the use of pure tones facilitated the comparison of tinnitus pitch among subjects receiving different acoustic therapies and the tracking of its variation across time (see later). During each tone sweep, the subject was asked to manually adjust the amplitude knob of the switchboard so as to keep the tone loudness approximately similar to the loudness of the tinnitus. Usually subjects reported more than one tone as matching the pitch of their tinnitus during both the upward and downward sweeps. In the latter case, subjects were asked to choose which one between the two tones (one having double the frequency of the other) best matched their tinnitus pitch.
The noise sequence was band-passed from 50 Hz to 15 kHz and equalized to compensate for the low-frequency bias of the frequency response of the earphones used for sound stimulation (see later).
The acoustic stimulation of the WN sound therapy was white noise in the frequency range 0.05-15 kHz equalized as shown in the figure to compensate for the poor low-frequency response of the earphones (see Methods section for details). These procedures aimed at obtaining a balanced design with an approximately equal number of subjects treated with the experimental therapy and with the control therapies (WN or Wa) and, at the same time, avoiding any possible bias in the process of data collection owing to, for example, the differential treatment of patients by the experimenters because of the type of therapy assigned.
These noncompliant patients were not counted in the analysis, thereby reducing the sample to 49 patients.
For each visit, we noted the number of days (dd) elapsed from the date of the start of therapy (usually within 1 week from the first visit) and the date of the control visit.
This was necessary to ensure that each patient contributed only one measurement value (if available) to the class mean value.
Of the 49 patients who started acoustic therapy, 2 in the WWN group, 3 in the WN group, and 1 in the Wa group withdrew before the first control visit. However, in the WWN group, the decrease was large (about -12 dB, corresponding to approximately a 75% decrease), whereas in the two other groups, the decrease was negligible (around -2 dB, corresponding to approximately a 10% decrease). By contrast, in two patients receiving the control therapies, tinnitus intensity was initially increased by about 5 dB, showing only minor fluctuations during subsequent control visits.
Decibel units on the y-axis are mean values (+1 SE) of ∆dBt computed for three subsequent temporal classes using dBt measurements in subsequent control visits of the same patient. 4 for an example) and no change of tinnitus loudness in the subject who was initially assigned to the WN therapy. Thus, our sound therapy (WST) was tailored to the frequency characteristics of patients' tinnitus. Indeed, analysis of the percentage of those withdrawing from each treatment group indicates that the WN therapy is the least tolerated, whereas the WWN therapy is the best tolerated by patients.
Third, in a few patients reporting subjective beneficial effects by the Wa therapy, the measure of the tinnitus loudness did not vary appreciably over the study period. The purpose of TRT is the reduction of the alarm reaction associated with the tinnitus sensation by altering the connections between the limbic and autonomic nervous systems (responsible for the alarm reaction) and the auditory system [5]. Conversely, tinnitus pitch is often located inside the hearing loss region toward the audiogram's edge frequencies, a phenomenon having strong analogy with the one described for the occurrence of the Zwicker tone using notched noise [22]. A comparison of variability among measurements of subjective tinnitus and objective stimuli. Psychoacoustic characterization of the tinnitus spectrum: Implications for the underlying mechanisms of tinnitus.
Acoustic communication in two freshwater gobies: Ambient noise and short-range propagation in shallow streams. Fortytwo hyperlipidemic patients with subjective tinnitus and hearing loss due to noise exposure were enrolled for the study. It has been reported that high-plasma cholesterol and triglyceride levels are one of the major risk factors for the development of occupational hearing loss [3-5]. It seems that noise and other metabolic disturbances have a synergistic effect on the development of tinnitus and hearing loss [5]. A diagnosis of acoustic trauma was verified by an ear, nose, and throat physician according to a clinical history of chronic noise exposure in patients who sought medical help for complaints of tinnitus and high-frequency hearing loss. Patients who had chronic otitis media or middle-ear effusion, those with an abnormal ear drum (perforation, retraction, etc.) or auditory canal, and those who had abnormal tympanometry (other than type A) were excluded. In the study, from 120 patients we chose 42 male patients (35%) with elevated cholesterol or triglyceride or both (age range, 19-60 years; mean age, 45 years). The patients were separated into two groups: the "unresponsive" group, made up of 22 patients who had no response to either of the therapies and still had hyperlipidemia, and the "responsive" group, consisting of 20 patients who had lower cholesterol or triglyceride levels. The results of the blood lipid profiles were withheld from the individual to prevent a placebo effect with the tinnitus therapy.
The significance of the difference in patient's comments on their tinnitus after the treatment ("same," "decreased," "increased," and "disappeared") was analyzed using McNemar and chi-square tests. However, the incidence of hyperlipidemia among a selected group of patients with neurosensory hearing loss varies.
They selected a group of subjects aged between 20 and 50 years and compared auditory thresholds at high frequencies and serum lipid levels.
Noise and metabolic disturbances have a synergistic effect on the development of tinnitus and hearing loss. Effects of experimental cochlear thrombosis on oxygenation: Auditory function of the inner ear. Direct effects of intraperilymphatic reactive oxygen species generation on cochlear function.
Clinical utility of LDL-apheresis in the treatment of sudden hearing loss: A prospective, randomized study. The relation of hearing in the elderly to the presence of cardiovascular disease and cardiovascular risk factors.
Appearance of free radicals in the guinea pig inner ear after noise-induced acoustic trauma. Progressive sensorineural hearing loss, subjective tinnitus and vertigo caused by elevated blood lipids. A comparison of auditory brainstem evoked potentials in hyperlipidemic and normolipidemic subjects. Exploration of the early auditory effects of hyperlipoproteinemia and diabetes mellitus using otoacoustic emissions.
Hypertension, hyperlipoproteinemia, chronic noise exposure: Is there a synergism in cochlear pathology? Effects of noise exposure and hypercholesterolemia on auditory function in the New Zealand white rabbit.
Hearing improvement after therapy for hyperlipidemia in patients with chronic-phase sudden deafness.
A prospective case-controlled study of 197 men, 50-60 years old, selected at random from a population at risk from hyperlipidemia to examine the relationship between hyperlipidemia and sensorineural hearing loss.
Purpose: The purpose of this study was to examine any potential benefit in lessening the severity of tinnitus in patients taking supplemental magnesium. However, many individuals have idiopathic tinnitus for which no specific cause can be determined. For example, the putative magnesium mechanism within the auditory system involves a metabolic cellular cascade of events.
The purpose of this study was to examine any potential lessening of the severity of tinnitus in patients receiving magnesium supplementation. The Tinnitus Handicap Inventory (THI) and Tinnitus Severity Scale (TSS) (Table 1), developed by McCombe et al.
A review by the Mayo Pharmacy indicated that there were no major drug interactions with magnesium at the levels of the current protocol.
Differences in TDR scores before and after supplementation were compared to determine any effect of supplementation on a participant's self-rated tinnitus. The adverse event data included the date of onset and whether the adverse event led to premature discontinuation of the intervention.
The THI was measured at the time of discontinuation if a patient discontinued the study before 3 months.
Treatments consisted of application of intravenous pentoxifylline, lidocaine, or vinpocetine (Cavinton) and combination of these agents with physiotherapy and soft laser. Guidelines for inclusion of each patient into an appropriate treatment group are still missing. All patients had previously been treated ineffectively by various oral drugs [betahistine (Betaserc), extract of Ginkgo biloba [EGb-761], tanakan [Tebokan], cinnarizine-dimenhydrinate (Arlevert)], or their combination] for at least 6 months.
To those in the lidocaine group, we gave a daily intravenous infusion of 40 mg lidocaine hydrochloride plus 250 ml physiological saline for 10 days. According to audiometry, we had three subgroups: bilateral normal hearing, unilateral normal hearing, and bilateral hearing loss. The output classification tree divided the patients into groups according to the metrics (Fig. As we compared the groups of either Cavinton or lidocaine infusion alone with groups who received one of these agents combined with physiotherapy with or without soft laser, the effectiveness of combination therapy was assessed as being better. The combinations of lidocaine with RHB and with RHB plus soft laser were assessed by the classification tree as being effective for patients younger than 62 years who had tinnitus lasting for more than 15 months (Fig. We hope that our outcomes will be helpful for patients suffering from chronic tinnitus, and we encourage our colleagues to undertake further research. Neuroprotective drug therapy: A medical and pharmacological treatment for tinnitus control. Glutamate antagonists, steroids and antioxidants as therapeutic options for hearing loss and tinnitus and the use of inner ear drug delivery system. Vinpocetine prevents 4-aminopyridine- induced changes in the EEG, the auditory brainstem responses and hearing. The inhibitory effect of intravenous lidocaine infusion on tinnitus after translabyrinthine removal of vestibular schwannoma: A double-blind, placebo-controlled, crossover study.
Transmeatal cochlear laser (TCL) treatment of cochlear dysfunction: A feasibility study for chronic tinnitus. Therapeutic results of steroid targeting therapy to the inner ear were evaluated in 3,978 ears of 3,041 patients. At the beginning of our clinical trials of this system, we used 4% lidocaine hydrochloride to alleviate distressing inner-ear symptoms of tinnitus, recruitment, fullness or stiffness in the ear, and vertigo. Dexamethasone, 2 or 4 mg, was introduced into the middle-ear cavity through a fine needle, just as is done in tympanic puncture. The severity or annoyance of tinnitus before the injection was regarded as being at level 10, and the level after the injection of drug was expressed as a score from 1 to 10.
In contrast, the effec-tiveness of our therapeutic regimen on tinnitus accompanied by streptomycin deafness was 48% and, in the presence of head injury, this figure dropped to 42%.
Overall positive effects on tinnitus were seen in 75% of cases immediately after intratympanic dexamethasone perfusion and in 68% after 6 months. In Meniere's disease, steroid injection to the middle ear might improve endolymphatic hydrops.
This review reveals no compelling evidence suggesting the efficacy of any pharmacological agent in the treatment of tinnitus. In that year, it was the third most prevalent disability among veterans, after hearing loss and generalized musculoskeletal disability. Therefore, therapy tends to be individualized and can range from placebo to surgery, with a multitude of options found between.
Thus, the potential for a safe and effective oral pharmacological intervention has the hope of offering widely accessible and acceptable treatment for tinnitus patients.
Most recently, Seidman and Babu [7] reviewed the role of alternative nutritional and medicinal treatment. Though these claims may be based on some science, their marketing and manufacturing is minimally regulated, with side effects and drug interactions poorly characterized. We supplemented sources by personal files and cross-referenced articles of the primary search.
We also gave attention to the presence of specific, defined outcome measures, including changes in audiometric tests or quality-of-life measures, such as the tinnitus handicap inventory (THI) [8].
However, a follow-up study from the same trial (and apparently the same data set) demonstrated a statistically significant decrease in tinnitusrelated disability via the multidimensional pain inventory (MPI) tinnitus interference questionnaire and in tinnitus loudness via audiometric matching at the frequency of tinnitus as compared with placebo [11]. Audiometric analysis was more consistent and typically involved pure-tone thresholds, speech discrimination, uncomfortable loudness levels, and tinnitus frequency and intensity matching. However, projections also occur via the dorsal and medial thalamic nuclei via the nonclassic pathway that subsequently projects to the amygdala and association cortices. The study lacked details of patient selection, crossover of treatment and placebo groups, and a discussion of the potential impact of drowsiness, caused by the sedating action of alprazolam, on loss of blinding. The gabapentin and clonazepam trial used SPECT imaging with 99Tc-HMPAO to identify increased perfusion in the medial temporal lobe system as evidence of treatment success.
Statistical power was alluded to in all trials, though not formally discussed, and was the subject of a critique on the study of prostaglandins in tinnitus [26]. However, the study did not include any statistical analysis comparing groups, offered no placebo, had a total of 20 subjects in each group, and was not blinded. However, a more recent study reported a statistically significant improvement in subjective rating of tinnitus both within the Zn2+ 50-mg daily treatment group and in comparison with placebo [35].
Finally, only 22 of 60 patients completed all phases of evaluation, although all subjects were analyzed on an intention-totreat basis. Studies with larger power, longer follow-up, and consideration for potential dependency are needed. In particular, the studies on misoprostol failed to show subjective improvements, and the clinical significance of decreased tinnitus loudness matching is doubtful. An experiment using a behavioral avoidance task during sound was able to reduce false-positive avoidance (presumably caused by tinnitus) with the use of N-methyl- D -aspartate receptor-blocking agents that may play a role as local therapeutics [47]. Specific selection, inclusion, and exclusion criteria should be presented, and convenience samples should be avoided. Outcomes that are likely to be clinically significant are those associated with a meaningful improvement in a patient's life. Statistical comparison of baseline characteristics of treatment groups should address any significant differences. As more than 70% of patients with noise-induced hearing loss also suffer from tinnitus, efforts to reduce the impact of environmental noise on hearing should continue, including the use of pharmacological agents. The ITJ benefited from his timely comments, criticisms, contributions of original manuscripts, and friendship.
Ascutney Hospital staff from 1988 to the present and of Alice Peck Day Memorial Hospital staff from 1992 to the present.
Public Health Service, the New Hampshire and Grafton County Medical Societies, the New England Otolaryngological Society, the New Hampshire Foundation for Medical Care, the New Hampshire Society of Otolaryngology and Maxillo-Facial Surgery, the Society of University Otolaryngologists - Head and Neck Surgeons, the Hitchcock Foundation, SENTAC, the American Otological Society, the American Neurootological Society, the American Rhinologic Society, Alpha Omega Alpha Honor Medical Society, Societas Baranyensis, the Neurootological and Equilibriometric Society Reg, and the New England Medical Association. He was a member of the Lake Mitchell Trout Club, the Montshire Speed Skating Club, and for 31 years an enthusiastic member of the Geriatric Adventure Society.
For many years, he participated in the Canadian Cross Country Ski Marathon, most recently on February 12 and 13, when he skied 60 miles. Maybe he was a closet overachiever and pushed himself too hard, but I was particularly impressed with his health and fitness activities: his eight-day cross-country ski trek across Green-land and all his other physically demanding activities - biking, hiking, skiing, running, and the like - which he did to the max. I know that his wonderful wife, Joan, and family will concur that this was a very typical evening's activity at the Weiders. Whatever he thought would be the most help and least risky for his patients was the course of action that he inevitably recommended.


The town was filled with Dudley's friends and patients (most of whom had apparently become his friends). When we parted at the end of each conference that we attended, we looked forward to meeting again in the following year, and we repeated that pattern every year.
He loved skiing, rafting, mountain climbing, bushwalking, cross-country skiing, and much more. As pleasant, friendly, and easygoing as he was, he had little tolerance for bureaucratic haggling and made no effort to curtail those feelings. I believe it is these qualities that were the key to Dudley's inspiration and success in diagnosing and treating clinical conditions, the management of which eludes others. Through lumbar puncture, Dudley proved that the answer was chronic intracranial hypertension and that this rendered the ear prone to fistula. Some of his successes were in those persons who also suffered from supposedly intractable dizziness and tinnitus. First, we classified the 10,000 patients into those suffering from the basic tetrad of tinnitus forms: bruits, endogenous (maskable) tinnitus, exogenous (nonmaskable) tinnitus, and other syndromes such as the slow brainstem syndrome.
Patients with a maskable or endogenous tinnitus prefer covering up their tinnitus by external sounds. We found typical shortenings in the latencies of the vestibular evoked quantitative electroencephalography (QEEG), an enlarged DC shift of the vestibular evoked QEEG, and typical cortical electrical burst expansion in three phases on the brain surface as shown by BEAM. First we recorded a thorough neurootological history with a systematic preprinted history scheme of Neurootologisches Anamneseschema Claussen (Neurootological History Scheme). As the sum of all the tinnitus spots being masked amounts to 141.74%, we were able to derive that nearly one-half of the sample suffered from a bilateral maskable tinnitus. The majority of patients (consistent through all age groups) reported so-called whiplash-related tinnitus problems after a car accident. The frequently reported sensation of a roaring in the right or the left ear occurred in only 0.13% (left ear) in our sample. In Vertigo, Nausea, Tinnitus and Hearing Loss in Central and Peripheral Vestibular Diseases .
In JM Aran, R Dauman (eds), Proceedings of the Fourth International Tinnitus Seminar, Bordeaux, 1991 .
In these cases, the speech discrimination measurements carried out in the quiet surroundings of the audiologist's office apparently do not correspond with the patient's hearing sensitivity in real life. Level 5 represents the primary auditory cortex and the cortical centers responsible for active acoustic selection.
In extensive investigations in the late sixties and beginning of the seventies, Spoendlin [3,4] identified the entirely different functions of the outer and the inner hair cells and of their various nerve supplies. The interacting function of the outer hair cell layer has the effect of a "cochlear amplifier" responsible for the sensibility of the inner hair cells in the hearing level range of approximately 0 to 40 dB.
As a result, an accompanying ascending degeneration of the hearing nerve was verified by measurements of a reduced action potential density in the hearing nerve that correlated with noise exposures lasting several weeks to months in three groups of subjects.
Group 1 included persons aged 10 to 19 years; group 7 included persons aged 70 to 79 years. Routine follow-up examinations of sensorineural hearing loss often reveal a considerable discrepancy between the two ears (Fig. We found, as an example, in a patient with congenital unilateral deafness an abnormally reduced reverberation ratio in the contralateral normal-hearing ear, which indicates a certain central compensation of the unilateral impairment. Moreover, the best of these tests correspond to the patient's hearing capacity in real-life situations.
A new approach to the physiology of hearing and the functional and differential diagnostic test. We found a significant long-term reduction of tinnitus loudness in subjects treated with notched noise but not in those treated with control stimulations. However, the physiological mechanisms and persistence of the sensation of the tinnitus have still not been fully clarified.
Indeed, anecdotal clinical evidence suggests that the exacerbation of the tinnitus sensation by exposure to sounds comprising the tinnitus frequency is a common complaint from patients suffering from tinnitus. Initially (first visit), each participant subject received an audiogram and tinnitus loudness and pitch-matching tests. In such cases, we instead used narrow-band noise (NBN) of one-third of an octave, having a pitch similar to the tinnitus frequency (according to patient judgment) of tones.
It must be stressed, however, that during the loudness-matching test, no effort was made to obtain the best match to tinnitus pitch, this being determined in a separate, experimental test (see later). Of course, the perceptual quality of a tone stimulus seldom corresponds to subjects' tinnitus sensation.
The frequency values identified by the subject in the two sweep tests were grouped and ordered from the lowest to the highest. It might happen that the patient was undecided about the two alternatives when these were of similar frequency.
Wa stimulation was an 8-minute sequence of stream noise recorded underwater with a hydrophone placed close to a stream cascade [16] (see Fig. Patients were also asked to regulate the listening volume to a level approximately matching the loudness of their tinnitus. In such cases, the patient usually informed the experimenters about the change that occurred.
Six subjects felt annoyed by the therapy and refused to continue before the first control visit (see Results).
If these subjects are included in the total count of patients treated, the number voluntarily withdrawing from the therapy in the WWN, WN, and Wa groups amounted to three, four, and seven, respectively, the highest percentage being in the WN group (about 30% of subjects) and the lowest being in the WWN group (about 15% of subjects; Fig. Figure 5 reports the variation of the mean value of ΔdBt, with time elapsed from the start of the therapy, for the three groups of patients.
Decibel units on the y-axis are values of ∆dBt computed using dBt measurements in subsequent control visits of the same subject (date on the x-axis).
We tested the effectiveness of the therapy using two types of control sound treatments: nonnotched noise (WN) or waterfall noise recorded underwater (Wa).
However, the WWN group had the lowest percentage of those who withdrew (around 15% of subjects compared to 28% in the WN group and 23% in the Wa group) among the three treatment groups, suggesting that WST was the sound therapy best tolerated by patients (presumably owing to the lack of annoyance caused by the stimulation of the patient with frequencies similar to that of the tinnitus). Thus, WST determined an objective and significant reduction of patient's tinnitus loudness and, hence, it appeared to be an effective sound therapy for the treatment of tinnitus. Therefore, to the extent that these differences might correspond to a different listening behavior by patients in relation to the sound therapy they received, the decrease of tinnitus severity observed among the group of patients receiving the WWN therapy could partly be explained by their (supposed) higher tolerance and stamina in motivation to listen to the therapy as compared to patients receiving the control therapies.
Likewise, other patients treated with the WWN and reporting no subjective improvement of their tinnitus sensation showed in fact a decrease of tinnitus loudness measured over time.
Therefore, the observed effectiveness of the WST in reducing tinnitus loudness appears consistent with the neurophysiological model of tinnitus underlying TRT [5]. One possibility is that Wa stimulation had poor masking effects on tinnitus in most patients, implying that the alarm reactions induced by tinnitus persisted in Wa-treated subjects.
Thus, a conceivable hypothesis is that a stimulation of the edge frequencies, but not the tinnitus region, by the noise frequencies just below the notched region has occurred during the listening of the WWN sound treatment. All patients who were required to complete the questionnaire and who were subjected to clinical examination were military personnel. A pure-tone signal was presented continuously at 50-Hz intervals at between 10- and 20-dB levels.
We placed all these patients on a low-cholesterol diet or antihyperlipidemic therapy (Table 2). When patients were asked to qualify the severity of their tinnitus, 10 rated their tinnitus as the same (47%), 9 rated it as increased (42%), 2 rated it as decreased (9%), and 1 patient had no tinnitus (2%). Lowry and Isaacson [12] reported 20% hyperlipoproteinemia among 100 patients with bilateral hearing loss.
Lipidosis of the inner ear has been postulated by Nguyen and Brownell [33] as an alternate mechanism. Insufficient perfusion of the cochlea due to increased blood viscosity and microthrombosis related to hyperlipidemia has been claimed to cause susceptibility to noiseinduced hearing loss [35]. We found in our study that the incidence of hyperlipidemia among patients with noiseinduced tinnitus and hearing loss was 35%. Characteristics of tinnitus and etiology of associated hearing loss: A study of 123 patients. Research Design: The study was a single-arm, open-label, before-and-after study of oral magnesium (532 mg per day) in 26 patients for 3 months. Although often presenting in conjunction with hearing loss, the magnitude of hearing loss does not necessarily correspond with the severity of tinnitus. Specifically, magnesium deficiency leads to increased permeability of the calcium channel in the hair cells with a consequent over-influx of calcium, an increased release of glutamate via exocytosis, and overstimulation of N-methyl-D-aspartate receptors on the auditory nerve fibers. In addition, all participants completed another THI after 3 months of magnesium supplementation. The mean hearing thresholds and mean TDR scores before and after treatment were assessed using a paired t test. For the subjects lost to follow-up, we assumed for the purposes of this analysis that there was no benefit from treatment. Effect of various serotoninergically induced manipulations on audiogenic seizures in magnesium-deficient mice.
Influence of dietary magnesium on the amplitude of wave V of the auditory brainstem response. Guidelines for the grading of tinnitus severity: the results of a working group commissioned by the British Association of Otolaryngologists, Head and Neck Surgeons, 1999. In our study, we evaluated some of the current treatment modalities to define the most effective for a certain group of patients. The Cavinton-plus-physiotherapy (Cavinton-RHB) group received a daily intravenous infusion of 20 mg Cavinton plus 250 ml physiological saline, and oral Cavinton 2 Χ 10 mg, combined with physiotherapy (soft techniques, including temporomandibular joint massage), the entire procedure lasting 20 minutes once daily for 10 days.
We crossed all boundaries that are created as a midpoint between all recorded numerical data on all metrics and sought maximized homogeneity.
1) treated by lidocaine (contains lidocaine infusion, lidocaine-RHB, and lidocaine-RHB-soft laser groups) or by Cavinton (contains Cavinton, Cavinton-RHB, and Cavinton-RHB-soft laser groups). Tinnitus improved in 75% of these patients immediately after treatment and in 68% after 6 months. Although the injection of 4% lidocaine hydrochloride is very effective for controlling inner-ear problems, patients complained of vertigo for several hours after the injection of medicine [2]. Before the procedure, the patient was asked to try to hold his or her posture steady and to avoid swallowing during the injection and for approximately 15 minutes thereafter to prevent the escape of dexamethasone through the Eustachian tube. A level of 0-2 for the residual symptoms represented good effects, 3-6 represented fair effects, and 7-10 represented poor effects.
The improvement of tinnitus with labyrinthine hydrops was good, but effectiveness for noise-or druginduced tinnitus was poor.
It appears that, to some degree, tinnitus control via our therapeutic regimen remained constant. Takahashi K, Ohtsu K: Pathology and treatment of cochlear tinnitus by blocking with 4% lidocaine and dexamethasone infusion. Analysis of prior investigations provides insight to appropriate methods for future work, which are outlined. Auditory disabilities taken together resulted in more than $1 billion of payment by the US Department of Veterans Affairs in fiscal year 2004 alone [2].
Finally, consensus on accepted outcomes for treatment is lacking, owing to the subjective nature of tinnitus. This form of therapy can be self-administered and selfmonitored, reducing the impact on medical resources for treatment. Although not establishing consensus, these studies identified some agents with promise, but the lack of uniform symptom definitions, outcome measures, and statistical power of the studies reviewed renders interpreting these conclusions challenging. Thus, the pharmacological treatment of tinnitus remains a realm of pseudoscience and supplements. We reviewed studies for basic and clinical science evidence for the pathophysiology and treatment of tinnitus, symptom definition, outcome measure, statistical power, and potential for future research.
Both studies highlighted the effectiveness of nortriptyline treatment of the depression associated with the tinnitus. This nonclassic pathway receives somatosensory input, which may be abnormally redirected to auditory regions of the central nervous system and perceived as tinnitus [14].
Baclofen (Lioresal), a GABA analog with binding to the GABA-B receptor, was found to be no more effective than placebo in a double-blind, placebo-controlled, prospective trial [19]. Statistical power was specifically mentioned in the Lioresal trial, as 90 patients were calculated as the minimum number necessary to afford a power of 80% to detect a clinically significant difference between treatment groups.
The other two studies were prospective, double-blind, placebo-controlled trials by the same authors in different patient populations with similar results. A recent novel study compared subcutaneous periauricular injections of botulinum toxin A with placebo in a double-blind, prospective, crossover, randomized, controlled trial and reported significant differences between groups along with a significant decrease in THI scores between pretreatment and 4-month post-botulinum toxin A therapy [28].
The remaining trials showed no benefit as compared to placebo, and each had unique features that merit review. This was a large trial involving age, gender, and duration-of-symptoms matching analysis that revealed no differences in subjective rating scales of loudness, annoyance, and quality-of-life impact.
Discussion of statistical power along with recruitment of adequate subjects was obtained in two studies [41,42], both reporting no effect of treatment.
These models have advanced our understanding of tinnitus as a central phenomenon and can be used to refine the exploration for effective pharmacotherapy. Benzodiazepines may prove to be counterproductive in the long run if suppression of neural plasticity is indeed something that will prevent reconditioning of nonclassic auditory pathways, as theorized in tinnitus retraining therapy [4].
However, these studies were also underpowered and did not address quality-of-life outcomes that may be evident with treatment. However, more standardized definition of zinc deficiency along with higher-powered studies are needed to address this potential treatment.
At best we can say that no benefit has accrued for the given dose and extract used in these studies. Riboflavin (B12) deficiency was demonstrated in sufferers with noise-induced hearing loss and tinnitus as compared to those without tinnitus. Very likely, different treatments for tinnitus will emerge for different groups of patients on the basis of comorbid illness and tinnitus duration, severity, or location.
Small improvements may be meaningless to those with mild tinnitus but very important to those whose tinnitus is disabling.
At the end of his residency, he returned with his family to Alaska as a staff physician at the Alaska Native Medical Center in Anchorage, where he became the chief of otolaryngology. He was a delegate to the Board of Governors of the American Academy of Otolaryngology and Head & Neck Surgery, Inc., from 1985 to the present, a member of the Prosper Meniere's Society from 1994 to the present, and a councilor to the executive committee of the New England Otolaryngology Society from 1998 to the present. Two years ago, he purchased a folding bike so he could take it with him wherever he went, including the lakes region of Italy. Despite his professional commitments, he always managed to support his children and grandchildren in their activities. At the annual Prosper Meniere's Society (PMS) winter meetings, he always organized a crosscountry ski day for all those who did not downhill ski. His family willingly gave up some quality time with him because they knew how important giving of himself to his patients was for him. His patients loved and adored him and always brought him something special when they came to the clinic visits.
Dudley was looking forward to attending the Thirty-Second Annual Meeting of the Neurootological and Equilibriometric Society in Melbourne, and we had plans to see the outback of Australia together with his wife, Joan.
He used to get up early in the morning, while we were still asleep, to climb Buttermilk Mountain in Aspen. Dudley served as a role model not only in how to relate to patients but in how to balance life's many responsibilities.
It is ironic that he passed on participating in strenuous physical activity, doing one of the things he loved.
He would often present his work each year at the International Tinnitus Forum, making exciting observations. It is true to say that others had come to a similar conclusion; the difference is that Dudley's goal was to research and publish on this condition and its treatment.
I think Dudley knew that ventricular shunts would have wider application than that of perilymphatic fistula. I would make him run through his most recent adventure in great detail, thereby making me a vicarious world traveler. Next, we examined all the patients otologically, including bilateral microscopical inspection of the outer ear, ear canal, and tympanic membrane. They also reported posttraumatic complaints of whiplash injury (also consistent through all the age groups but especially frequent in the age group 30-40 years). Significantly different from the group identified as having endogenous tinnitus are the behavior and the sensation of those with exogenous tinnitus or nonmaskable tinnitus, who find relief in a completely silent environment. The majority of our patients described their tinnitus as lasting from one to several years (as seen in Fig. We found that 3.70% of patients complained about a reduced acuity in their taste (hypogeusia).
The correlations between the pure-tone threshold levels and the speech comprehension ability, which are gathered easily from the alphaJ value for speech hearing loss (gap between the scores for normal two-digit numbers and pathological numbers on the 50% line) in the speech audiogram, mainly refer to the tone frequencies 500, 1,000, and 2,000 Hz.
These findings and the conclusions drawn from them opened new dimensions in the field of hearing physiology.
Functional outer hair cells produce otoacoustic emissions (OAEs) [7], which are assessed routinely in an objective test that is both reliable and practical.
In group 1, after 6 and 7 weeks of impulse noise exposure, the result was cross-sectional damage to the hearing nerve of 10.6%. The discrimination curves derived from the normal Freiburg test material are in relatively close correspondence up to age 60, whereas the curves for groups 6 and 7 are slightly diverging. These results point to the importance of the personalized sound treatment of tinnitus sufferers for the development of an effective tinnitus sound therapy. This observation has been the foundation of our approach to the treatment of tinnitus and the key element for the development of an effective personalized sound therapy. This may partly explain the high betweensession variability of pitch-matching measurements often reported in the literature [11-13].
Therefore, before testing the patients for the first time, they were instructed in how to use the apparatus and make the tinnitus pitch-tone comparisons. This occurred frequently, as many subjects identified matching tones of similar frequency during the upward and downward sweeps. We note that the distinction made here between single- and multi-pitched tinnitus was intended solely for the development of an appropriate tinnitus therapy; it may or may not have a relationship with the internal spectrum of the tinnitus. Therefore, the noise energy between the two broken lines is missing in the WWN sound therapy. In case of marked hearing loss in one ear, subjects were advised to regulate the listening volume using the ear of best hearing. Conversely, the key feature of the WWN therapy is the construction of a noise window around the tinnitus pitch, implying that the window features should track any observed change (real or supposed) of the value of F t . Thus, sound stimulation of patients of the two control groups was not personalized on the basis of frequency characteristics of patient's tinnitus. Possible sources of between-session variability of pitch matches are, for example, the multipitched nature of many tinnitus percepts [13], the change of tinnitus pitch with time after application of the sound therapy [10] (Lugli et al., unpublished data), or judgment errors by patients.
However, the observation that many of these subjects experienced tinnitus relief by listening to the water noise soundtrack (Lugli et al., unpublished data) does not support this interpretation. In addition, activation of the mechanism underlying the Zwicker tone must have occurred in patients listening to the WWN treatment, although none of them reported such an aftereffect, presumably because of the pitch similarity between the Zwicker tone and the tinnitus percepts. We excluded on the basis of their response to the questionnaire or clinical examination subjects who had a history of familial hearing loss, head trauma, collagen disease, neurological or hormonal disturbance, addiction to alcohol, or ototoxic drug therapy.
The main criteria for response to the antihyperlipidemic therapy was defined as a return to normal cholesterol or triglyceride levels after therapy or at least a 40% drop from either of the initial blood cholesterol or triglyceride levels if the values were slightly above the normal limits.
The latter authors showed that the lateral wall of outer hair cells from guinea pig cochlea incorporates water-soluble cholesterol. Axelsson and Lindgren [34] matched 78 men at age 50 years with high serum cholesterol levels to 75 randomly selected 50-year-old men and found significant correlation between noise exposure and high cholesterol level.
Tinnitus severity was evaluated and recorded daily by the patient using the Tinnitus Distress Rating (TDR) scale of 0 (no tinnitus) to 10 (worst possible tinnitus). Recent studies of both noise-induced hearing loss and idiopathic sensorineural hearing loss have suggested that magnesium supplementation may lessen the severity of tinnitus in patients. The THI scores were converted to the grades of the TSS for the purpose of categorizing the numeric values of the THI into a reliable 5-item grading scheme. These participants were included because if noncompleters doing poorly enough to drop out were not analyzed, then selection bias would be likely.
The aim of our study was to compare treatment modalities and define their effectiveness for tinnitus relief. For the Cavinton-RHB-soft laser group, we administered a daily intravenous infusion of 20 mg C Those in the lidocaine-RHB group were given a daily intravenous infusion of 40 mg lidocaine plus 250 ml physiological saline, combined with physiotherapy, for 10 days. When we finished dividing by all metrics (or when it was superfluous to continue with such division), we decided on classification of terminal leaf by the bayesian method. We did not find any additional effect of soft laser, but we expect that the effect of soft laser on biostimulation cannot be observed during 10 days of therapy. However, when tinnitus is continuous and loud, it can interfere with a person's quality of life and may be so annoying as to incite neurosis. The ma-jority of the patients could not be treated successfully by oral administration of vasodilators or mild sedatives.
Accessible, efficient, and effective treatment for this potentially disabling symptom remains elusive. All these issues lay the foundation for a heterogeneous body of literature on the topic that is largely devoid of compelling evidence for any particular treatment protocol. Additionally, such therapy may also benefit by reducing the causes of tinnitus and not just providing symptomatic relief.
Further complicating matters is that largescale, well-controlled clinical trials of pharmacological agents are expensive and time consuming if conducted properly. Compared to placebo, amitriptyline demonstrated a statistically significant decrease in a subjective measure of tinnitus intensity in a single-blind prospective trial [12]. Subjective outcomes ranged from a simple yes or no response to the question, "Has your tinnitus improved?" [10] to longer multipart questionnaires, such as the Iowa Tinnitus Handicap Questionnaire [11]. Salicylate toxicity, a known cause of reversible tinnitus in humans, also results in GAD upregulation and increased GABA receptor affinity in the inferior colliculus of rats [15]. The study did demonstrate a statistically significant improvement on the THI within the treatment group, but this was not considered clinically significant, and treatment was associated with significant side effects leading to withdrawal from the study by 26% of participants. The studies found a statistically significant decrease in loudness matching and a statistically insignificant decrease in subjective rating of tinnitus in patients with hypertension or diabetes mellitus (or both) [24] or the absence of systemic or other known otological disease [25]. The study identified having limited power, with a total of 26 subjects completing injections and follow-up, and the differences in groups incorporated those improved, those worsened, and those unchanged, without specifically addressing the statistical difference in improvement alone. Two additional, nonplacebo- controlled studies investigated the incidence of zinc deficiency in patients with tinnitus along with the potential for improvement with zinc replacement. However, this study was done completely by mail or phone, and no physical or audiometric evaluation was performed on patients. Another GABA-active drug, baclofen, showed promise in a limited animal study, although the single clinical study with significant design limitations demonstrated no better efficacy than that of placebo. Effective definition of the study population will enable important post hoc analyses to reveal these potential treatments. Visual analog scales are useful but should record variables of annoyance and awareness in addition to simply loudness.
In preparation for his adventures, he often mowed the lawn with a pack filled with rocks on his back. A member of the Mixed Nuts Supper Club, he loved having people over to his home for dinner. He personally made sure that everyone participated, made sure that they got the right-fitting shoes and skis, gave each and every new skier a personal lesson, and started each one out by his side to guarantee that they were okay. He was scheduled to present three papers on topics that had captured his interest over the last years: perilymphatic fistula, deep-ear pain, and perilymphatic hypertension.
He would then attend the morning scientific session, sit down as close as possible to the presenter of a paper, take off his shoes, and doze off, only to be alert and present when the discussions started.
Dudley's sincere, caring devotion has touched his patients to a degree that will remain an inspiration to all of us who are fortunate to have known him.
He seemed to be close to a significant breakthrough, or perhaps he had made one that was beyond our ability to comprehend.
Car accidents and whiplash occur more frequently in the younger age groups, whereas reports of cerebral concussions are more frequent in the old-age group (> 70 years). Finally, via our complex neurootometric tests, we demonstrated slowing deregulations in the statoacoustic pathways. We heard no complaints about trigeminal disorders; however, we found both peripheral and central facial nerve paresis, though in a small number (see Fig.
28) played a minor role in our sample, as was evident for the major hormonal diseases (Fig. However, in cases of minor and medium basocochlear inner ear hearing loss, the hearing loss of speech usually is damaged only slightly.
Consequently, the outer hair cells, being by far the more sensitive hair cells, have been shown merely to steer the tuning of the sensibility of the inner hair cells. In group 2, after 17 and 19 weeks of impulse noise exposure, the damage amounted to 27.2% of the cross-section of the nerve, which is a significant increase. By comparison, the distorted discrimination scores show decreased values on the whole but also are in close correspondence up to age 60.
Also, at regular checkups of patients with noise-induced hearing loss, the onset and progression of ascending degeneration of the hearing nerve may be observed by means of the test [16].
In addition, no treatment can be considered efficacious in providing longterm relief from tinnitus in comparison to placebo [2]. In such cases, the operator continuously varied the knob of the tone generator within the narrow band delimited by the two frequency values to allow the subject to identify the tone best matching the tinnitus pitch. Hence, our results cannot be compared with those of studies trying to assess the form of the tinnitus spectrum [13].
As compared to the waterfall noise recorded in air, the waterfall noise recorded underwater is characterized by greater energy content at lower frequencies and larger amplitude and frequency modulation [16]. In the Wa sound therapy, most energy is concentrated in the lower part of the spectrum (bottom spectrum = mean spectrum of the 8-minute sequence of waterfall noise; see Methods). Thus, ideally, patients subjected to the WWN therapy should receive a new windowed noise sequence almost each time at every control visit. Thus, the overall number of subjects available for the comparative analysis of data was of 43 patients, of whom 20 were treated with WWN, 11 were treated with WN, and 12 were treated with Wa. We did not attempt the chi-squared analysis of the proportion of those who withdrew in the three groups owing to the low number of those who withdrew, expected in each group under the null hypothesis. Though the reliability of the method of pitch assessment proposed here awaits further testing before being asserted, our findings nonetheless point to the type of pitch-matching procedure adopted as a major factor responsible for the unreliability of pitch estimates documented in the tinnitus literature [18]. These facts do not support a supposed presence of marked differences in the at-home use of the therapy by patients of different treatment groups. One or both of these phenomena might have determined a reorganization of the neural activity of the edge frequencies resulting in the observed longterm reduction of the tinnitus percept in such patients.
We also thank all personnel in the audiological laboratory of the University of Parma for their invaluable contribution to the collection of clinical data. The difference between tinnitus scores in the unresponsive and responsive groups and the change in tinnitus scores before and after therapy in the responsive group were significant. None of the patients had cerebrovascular disease, hypertension, electrolyte imbalance, cranial nerve deficit, or clinical signs of peripheral neuropathy. Then, the pitch-match frequency threshold of the tinnitus was measured as the tinnitus loudness match of the pure-tone stimulus presented with a 1-dB increase of tinnitus frequency. Morizono and Paparella [30], using cholesterolfed rabbits, showed increased auditory dysfunction with time at all frequencies.
This uptake of cholesterol is accompanied by an increased stiffness of the cells, which may impair the cells' electromotile response.
Enhancement of cochlear action potentials and auditory brainstem responses has been demonstrated after limited intake of cholesterol. However, patients were at the chronic phase, more than 1 month from the onset of the hearing loss. The Tinnitus Handicap Inventory (THI) was administered before and at the end of the study, and scores were converted to the grades of the 5-item Tinnitus Severity Scale (TSS).
This relationship suggests these processes may be linked by underlying imbalances at the level of the hair cell. Magnesium improved hearing recovery and lessened tinnitus in patients with idiopathic sudden hearing loss (Gordin et al., 2002). Therefore, subjects with no follow-up were treated as though they had no improvement and were included in the analysis. To those patients in the lidocaine-RHB-soft laser group, a daily intravenous infusion of 40 mg lidocaine plus 250 ml physiological saline, combined with physiotherapy and soft laser (for softlaser specifications, see earlier in this paragraph), were given for 10 days. The improvement of tinnitus in the presence of labyrinthine hydrops was good, whereas the effects on noise-or drug-induced tinnitus were poor. Some patients with an inner-ear problem experience such overwhelming tinnitus that they would "cut off their ear" or "poke a hole in it with an ice pick" to try to relieve the noise. Depending on the clinical situation, some patients received a second course of four injections 3 months after the first course. Much of the available clinical data, therefore, comes from small studies with significant design flaws.
However, comparisons were made before and after treatment within groups but not between groups. GABA inhibition at the level of the inferior colliculus in rats is also associated with development of audiogenic seizures [16].
A prospective study reported 90% improvement in those completing treatment with combined gabapentin and clonazepam in a select group of patients with severe, disabling tinnitus verified by decreased perfusion on SPECT imaging of the amygdala-hippocampus region [20]. The first study reported a significantly increased incidence of zinc deficiency in tinnitus as compared with healthy controls and a significant decrease on a subjective rating scale with Zn2+ 34-68 mg daily over 2 weeks [32].
The most recent randomized, controlled trial showed no significant improvement with Ginkgo biloba by itself and also no benefit when considered in a meta-analysis along with other trials in the literature [42].
The doses used in the studies were substantially lower than those demonstrating benefit in the animal model. Currently, no clinical study has used gabapentin alone, though this seems a logical choice for chronic therapy, given its limited side-effect profile and lack of addiction potential. In the last few years, he participated in Dartmouth track events, competing with the weight and hammer. The statistical results demonstrate that tinnitus is interconnected to a multifactorial disease background with a broad spectrum of individual complaints.
Only 0.13% of our patients described a subjective roaring sound in the left ear, whereas none attributed it to right ear.
In such cases, the visual acuity problems were corrected most frequently by use of eye glasses (74.50%). Group 3, measured 9 and 12 months after noise exposure, showed an almost identical value of 26.1 % cross-sectional nerve damage. However, a clear curve divergence is evident, especially in relation to the 50% words line, for groups 6 and 7. Hence, the width of the band-stop filter amounts to 1,377 Hz, being 5,462 Hz and 6,838 Hz, respectively, the lower and upper frequency extremes of the band, with the center frequency at 6,150 Hz.
This is admittedly tedious and perhaps of little therapeutic significance when the re-measured value of F t is similar to the last one determined in the previous session. To explore the efficacy of the WWN therapy further, three Wa subjects and one WN subject were chosen among the group of patients reporting no relief from the therapy and were asked to abandon the assigned therapy and to start with the WWN therapy. Finally, 7 of the 20 patients treated with WWN were given one (n = 5) or two (n = 2) updated WWN treatments during the study period (see Methods for details).
Hence, the lack of direct control by the experimenters over the patient's at-home listening behavior was unlikely to be a factor potentially affecting the main conclusion of this study about the effectiveness of the WST therapy in the treatment of tinnitus. It seems that the order of destruction and the high-frequency nature of the auditory dysfunction are correlated not only with the frequency and severity of the noise exposure but with the presence of the secondary pathology, as the formation of vasoactive lipid peroxidation products after intense noise is similar to the condition seen in metabolic damage to the organ of Corti [7,14-17]. In a survey of 44 patients with cochlear-type hearing loss, Booth [26] found hyperlipidemia in 28% of the men and 10% of the women.
These authors observed hearing improvement of more than 10 dB in 9 of the 12 patients after antihyperlipidemic therapy. The purpose of this phase 2 study was to investigate whether the treatment was effective at all, and, as such, a placebo control was not performed. The possible influence of magnesium and its antagonist, calcium, has been discussed in the literature as a contributing factor in the mitigation of noise-induced hearing loss, ototoxicity, and the hyperexcitability of the auditory system (Cevette et al., 2003).
Our results indicate that in high-tone tinnitus, the effects were poor, but they were good for low-pitched tinnitus. A retrospective look at SSRI use in patients with tinnitus reported a statistically significant improvement on a tinnitus severity index over time in 23 of 30 patients [13]. No discussion of statistical power was mentioned in any study, and studies involved between 19 and 92 subjects. In an analysis of inferior colliculus hyperexcitability, various GABAergic agents were found to have very different effects on modulating evoked potentials, suggesting agonist-receptor variability with potential clinical implications for treatment. However, improvement was defined on subjective analog scales from 0 to 7, no control or placebo was used, and the 30% of patients who dropped out of the study for various reasons were not included in analysis.
The second study found no strong relationship of zinc deficiency and tinnitus and failed to demonstrate significant improvement with Zn2+ 220 mg daily for 2 months, although a trend toward improved symptoms in elderly patients with hearing loss was noticed [36]. Many have been shown to reduce noise-induced hearing loss in animal models, and the effects are both peripherally and centrally mediated [45]. Again, widely recognized categorical scales and scored questionnaires that measure quality-of-life impact are recommended. He was always eager and willing to join any activity, from soccer with his children and grandchildren to headstand contests.
He did the same thing for any new members who were lucky enough to go downhill skiing with him. Finally, the topodiagnostics of the functional neurootometric analysis shows that this type of endogenous tinnitus constitutes decidedly more central than peripheral statoacoustic pathology. Astonishingly, even the number of occurrences of basic neurological disorders (paralysis, paresthesias, apoplexies, epilepsia, Parkinson's disease, and brain tumors) was very low (as shown in Fig. As regards the time-related behavior of ascending degeneration, the findings give evidence of an asymptotic process within given periods of noise exposure.
Here, the deterioration of distorted-speech discrimination ability in normalhearing persons beyond age 60 becomes evident.
The procedure was repeated until the tone identified up to that point was compared with the highest tone (F n) of the sequence.
Cursory examination of pitch match position in relation to the patient's audiogram showed that the matches were frequencies above that at the beginning of the region of hearing loss on the audiogram. The control-toexperimental therapy shift occurred after 3-7 months from the beginning of the experiment. In this manner, preventive measures may provide restorative support to the injured cochlea. We required all patients to rate their tinnitus from 1 to 10, with 10 being loudest (Table 1). All data were collected at Mayo Clinic in Scottsdale, Arizona, between March 6 and December 10, 2008. Permanent and temporary changes in auditory function have been linked to nutritional deficiencies of magnesium. Based on the results of the present study, the authors have initiated a Phase 3 study using a placebo and double-blinding to control for factors unrelated to the magnesium supplementation. None of the treatment modalities had an objective correlate of improvement, though improvement was reported by a visual analog scale. However, no control group was included, nor was mention made of when patients began SSRI use relative to their initial tinnitus severity index score. In those with normal hearing, zinc deficiency may play a role in the development of tinnitus, and zinc supplementation may be helpful in those cases [33,37]. Statistical analysis should compare effects within all treatment arms as well as between arms.
The high-frequency tinnitus often develops close to the C5 dip and can be masked below the hearing threshold (see Fig. Clearly, a typical interrelation of tinnitus with a single major disease group is highly unlikely. The goal is the reduction of subjects' tinnitus perception by providing competing auditory stimuli masking the tinnitus.
This observation agrees with results by earlier and recent studies on the relationship between tinnitus pitch and hearing loss [9]. Each level was defined by short explanations to simplify the patients' grading of their tinnitus.
Finally, single-photon emission computed tomography (SPECT) imaging has suggested a loss of GABA inhibition in the amygdalahippocampus formation in humans with tinnitus [17]. Though they may not prove useful in treating tinnitus, antioxidants may help to reduce the noise-induced injuries that precipitate tinnitus. There was no significant change in hearing thresholds from 250 Hz through 8,000 Hz for either ear during the duration of the study (Table 2).
Side effects of active and placebo treatment should be carefully documented and analyzed for possible effects on subjects discontinuing the trial. However, no firm experimental evidence supports the effectiveness of these methods in the long term: an objective reduction of the loudness of the tinnitus or the complete recovery from tinnitus.
Data Collection and Analysis: The main outcome measures were mean TDR scale scores and THI scores as converted to TSS grades. There was a significant decrease in the severity of tinnitus for subjects on the basis of their THI responses (P=.03).
Those patients whose THI scores translated to "slight" or greater grade on the TSS before the intervention showed a significant decrease in the severity of their tinnitus (P=.008) (Table 3). Figure 3 graphically represents the change in TDR in 26 patients from baseline to 3 months after treatment with magnesium. Conclusion: The results suggest that magnesium may have a beneficial effect on perception of tinnitus-related handicap when scored with the THI. After supplementation, by intention-to-treat analysis, 14 of 26 patients (54%) continued to have more than slight impairment; by analysis of patients who completed the study, only 7 of 19 patients (37%) had more than slight impairment.



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Comments to «Tinnitus journal articles free»

  1. pepsu writes:
    Treatment named re-instruction therapy - even though it won't make thoughts the occasional.
  2. canavar_566 writes:
    Sudden sensorineural hearing loss (ISSNHL), is created when audiometry confirms not removed path for permanent.