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Author: admin | 24.05.2014 | Category: Tinnitus Causes And Treatments

In desperate cases the auditory nerve of tinnitus patients was transsected, however this did not result in a reduction of tinnitus – what would be expected if the tinnitus were generated in the inner ear – but rather increased the tinnitus. This is evidenced by the fact that an increasing amount of tinnitus studies are published in the most prestigious neuroscience journals, but also by the impressive amount of high quality research presented at this year’s TRI meeting which was held under the motto “The neuroscience of tinnitus” and which had more interested attendees than could be accommodated at the conference site. This article aims to give an overview about the most recent advances in the understanding of the mechanisms involved in the generation of tinnitus and its comorbidies, but also about recent advances in the diagnosis and treatment of tinnitus. These studies are important since they demonstrate that tinnitus is a very frequent problem. Moreover tinnitus became a major political issue in the United States since Tinnitus and Hearing Loss are the most frequent health complaint of soldiers returning from Afghanistan and Irak resulting in yearly compensation payments for tinnitus and hearing loss of over 2 billion US $ per year (Yankaskas 2011).
Tinnitus is classified according to whether the perceived noise has its source within the patient’s body known as objective tinnitus or somatosounds (for example, myoclonic contractions of the tensor tympani muscle or blood vessels) or if it is only perceivable to the patient and lacks a specific sound source, namely subjective tinnitus.
The fact that tinnitus can have many aspects means also that the different forms have different underlying mechanisms and require different treatments. Animal models of tinnitus provide the possibility to exactly identify the neuronal mechanisms of tinnitus generation and to test the effects of various treatments. For example in animals it is possible to record electrical activity of different areas of the brain by inserted electrodes.
Many different functional and structural imaging techniques have been used to identify structures in the central nervous system which are believed to play an important role in the pathophysiology of many forms of tinnitus. The neuroimaging methods functional magnetic resonance (fMRI) and positron emission tomography (PET) enable to measure regional changes of cerebral blood flow, which in turn is an indirect measurement of neuronal activity. EEG and MEG have revealed consistent results across many studies in the sense that in tinnitus the normal activity pattern in the auditory cortex is changed. Even if neuroimaging studies have contributed largely to the understanding of tinnitus and have recently been shown to be useful for measuring changes in brain activity induced by successful treatment (Tass et al.
Most hearing problems are related to the inner ear and within the inner ear to the hair cells that are responsible for the transmission of high frequencies.
Whether the tinnitus signal is perceived as important and whether the attention focus is kept on the tinnitus, depends on activation of the salience network (De Ridder et al.
Noteably it is important that the different brain networks involved in tinnitus may differ from patient to patient, depending on the specific clinical characteristics.
In the last years valid assessment instruments have been developed for assessing the different aspects of tinnitus. These developments are essential to bring clinical tinnitus research on a methodologic level that will provide information which treatments are efficient on which aspects of tinnitus in which tinnitus subgroup. As mentioned before there are several forms of tinnitus which differ in the involved neuronal mechanisms.
Also in subjective tinnitus the etiology of tinnitus and comorbidities play an important role. Thus, various etiologic factors and comorbidities are known to play a role in tinnitus and most likely lead to specific pathophysiologic patterns of neuronal activity. Currently there is no pharmacological substance approved by the Federal food and drug administration (FDA) or the European Medicines Agency (EMA) for the treatment of tinnitus (Elgoyhen & Langguth 2010).
Thus, even if some drugs have been reported to provide moderate relief of symptoms in a subset of patients, no drug has yet proven sufficient effectiveness in randomized controlled clinical trials in order to be approved specifically for tinnitus. Very recently, coordinated reset stimulation (Tass & Hauptmann 2007) has been proposed for tinnitus treatment.
Among new pharmacological approaches the most promising results come from a large study that investigated the substance neramexane, which blocks both glutamatergic NMDA receptors and a9a10 nicotinic cholinergic receptors (Suckfuell et al. Recent neuroimaging studies have identified further brain areas that are involved in the distributed “tinnitus network” (De Ridder et al. The most studied approach has been rTMS to the temporal cortex, which has shown beneficial effects in several studies (Meng et al.
All techniques presented in this section have been only recently been developed as treatment options for tinnitus. A first effort has been made by a multidisciplinary and multinational team of clinicians (Langguth et al. This evidence-based treatment algorithm advocates a structured approach for the diagnosis and treatment of tinnitus, with particular emphasis on awareness of specific subgroups of tinnitus patients who might benefit from tailored treatment (Langguth et al. The presented algorithm for the management of tinnitus represents the essential structure of the recently edited   Textbook of Tinnitus which provides a multidisciplinary overview of the diagnosis and management of this widespread and troubling disorder.
Within the last years animal research and neuroimaging have generated a more and more detailed understanding of the pathophysiological mechanisms of the different forms of tinnitus.
Animal models and the first neuroimaging studies of tinnitus patients in the nineties demonstrated alterations in the central nervous system. These numbers may be helpful to convince both health authorities to perceive tinnitus as a health problem of high socioeconomic relevance and the health industry to invest in tinnitus research. Also here there is an increasing motivation in funding tinnitus research for developing more satisfying treatment options in the future. Objective tinnitus is very rare, but in some of the rare cases of objective tinnitus causal treatment is possible.
Tinnitus can take the form of continuous buzzing, hissing or ringing, or a combination of these or other characteristics. The acoustic aspect involves the phantom sound the unwanted sound; ie, most commonly known as the perception of ‘ringing in the ears’.
The methods that mimics best the situation in most tinnitus patients is the induction of tinnitus by noise trauma. There are very recent studies, which found behavioural changes in tinnitus animals that resemble those found in animal models of anxiety and depression (Zheng et al.
In the auditory cortex of tinnitus patients alpha activity is reduced, whereas delta and gamma activity is increased.
2011), neuroimaging has not yet been developped to a level that it would be useful in clinical diagnostics.
For example in noise induced hearing loss or age related hearing loss there is preferentially damage of the high frequency regions. Thus for example in people that are distressed by their tinnitus, the brain activity that is relevant for tinnitus perception is connected to increased activity in the distress network. Morfeover it has been systematically investigated which changes in these questionnaire scores are clinically relevant (Zeman et al. Antidepressants are commonly used in the pharmacological protocols for the management of tinnitus.

Music with individualized frequency composition has been proposed for the treatment of tinnitus (Stracke, Okamoto, & Pantev 2010). Based on computational modeling, individualized auditory stimuli above and below the tinnitus frequency are presented as short tones with the aim to renormalize tinnitus related pathologic neuronal synchrony.
The idea of this approach is to normalize the disturbed neuronal network activity that underlies tinnitus.
Even if they have shown promising results in pilot studies, none of them have supplied enough evidence for a general application in routine treatment. The book emphasizes that tinnitus is not one disease but a group of rather diverse disorders with different pathophysiology, different causes and, consequently, different treatments. Alterations in several auditory and nonauditory brain networks have been identified, which reflect the various clinical aspects of tinnitus and which interact dynamically with each other.
2011b, "Transcranial magnetic stimulation and extradural electrodes implanted on secondary auditory cortex for tinnitus suppression", J Neurosurg. 2010, "Sound therapy (masking) in the management of tinnitus in adults", Cochrane Database Syst.Rev. 2010, "Acoustic stimulation treatments against tinnitus could be most effective when tinnitus pitch is within the stimulated frequency range", Hear Res., vol. 2011a, "Contralateral parahippocampal gamma-band activity determines noise-like tinnitus laterality: a region of interest analysis", Neuroscience.
These findings initiated a paradigm shift in tinnitus research in the sense that research was not any more restricted to the ear but also included the central nervous system. Two large population based studies demonstrated that tinnitus occurs very frequently in the population. In order to deal with this situation it has been proposed to assess all potentially relevant clinical characteristics of tinnitus patients in clinical treatment trials and collect the data in large databases. Even more important the effect of therapeutic interventions on bain activity can be tested. Alterations in the central auditory pathways in tinnitus patients have been shown already 15 years ago.
Successful treatment reverses these abnormalities, indicating that they represent the neuronal correlate of tinnitus loudness. Specific patterns of brain activity have been identified as predictors for sprecific treatments (Vanneste et al. As a consequence less information of the high frequency part of sound is transmitted to the brain. A high salience of the tinnitus signal in turn may increase the perceived loudness of tinnitus by causing increased amplification of the signal in auditory pathways (Rauschecker, Leaver, & Muhlau 2010).
Moreover earlier findings that the brain activation patterns changes with increasing tinnitus duration have been confirmed (Schecklmann et al. Thus patients underwent treatments, even if no clear data were available that provided information about the efficacy of these treatments. Moreover tinnitus has many aspects, which may be of different relevance in different patients.
Moreover the development of methodological standard for clinical tinnitus trials will help to overcome a current barrier which hampers the investment of pharmaceutical companies in the tinnitus field: an internationally accepted standard for clinical trials will provide an orientation what will be required for the approval of newly developed tinnitus drugs.
In most cases hearing problems are involved in the etiology, but in many cases temporomandibular disorders or neck problems may cause tinnitus as well. In these meta-analyses the results of available controlled studies are pooled ans reanalysed.
The results of studies investigating antidepressants suggest that these compounds have no direct effect on the tinnitus, but that tinnitus patients with depression and anxiety may gain some benefit from them (Langguth et al. In detail the individually favoured music has been modified in the sense, that the frequency area around the perceived tinnitus tone has been removed. Whereas the classic indication for cochlear implants has been bilateral hearing loss, new studies demonstrated that unilateral cochlear implants can have very beneficial effects on tinnitus in patients with single-sided profound deafness with concomitant ipsilateral incapacitating tinnitus (Kleinjung et al. First attempts stimulated the auditory cortex, either by transcranial magnetic stimulation (Langguth et al. Being at an early stage of development, an increase in efficacy can be expected for all these methods in the next years, especially with increasing knowledge of both the pathophysiology of the different forms of tinnitus and the neurobiological mechanisms involved in the modulatory effects of the different interventions.
According to this algorithm, all patients initially receive the same diagnostic assessment, the outcomes of which are used to provide a tailored approach to subsequent diagnostic or therapeutic evaluations.
The Textbook of Tinnitus describes both the theoretical background of the different forms of tinnitus and it provides detailed knowledge of the state-of-the-art of its treatment.
This knowledge has resulted in new potential therapeutic targets and new treatment approaches, of which many have already shown promising data in „proof of concept“-studies. 2011, "Treatment of chronic tinnitus with repeated sessions of prefrontal transcranial direct current stimulation: outcomes from an open-label pilot study", J Neurol.
Moreover all treatment concepts that aimed to induce therapeutic changes in the inner ear failed to improve tinnitus. In addition there are emotional, cognitive and memory components of tinnitus that vary from patient to patient.
With these data it may be possible in the future to identify characteristics that predict successful treatment outcome for specific therapies (Landgrebe et al.
Very recent studies have demonstrates that tinnitus related changes of neuronal activity can be normalized by electrical brain stimulation (Zhang, Zhang, & Zhang 2010), specific drugs (Yang et al. However it has been only very recently that neuroimaging studies have systematically been used to differentiate the different forms of tinnitus (unilateral versus bilateral, pure tone versus noise like, with more and less distress, with shorter and longer duration) (Schecklmann et al. 2011), but more studies with large sample sizes will be needed in the future to find out, whether neuroimaging methods will have the potential to predict the success of different treatment interventions. The brain in turn tries to compensate for this reduced input and increases the gain of the internal amplifiers. This principally useful mechanism of the brain to amplify important information results in case of tinnitus in a vicious circle that contributes to the perpetuation of tinnitus.
One patient may be bothered by the loudness of the tinnitus, other patients by the annoyance or the insomnia the tinnitus causes. Standardized assessment of clinical characteristics together with systematical collection of these data in large databases (Landgrebe et al. A typical form of objective tinnitus is heart synchroneous pulsatile tinnitus, which is frequently due to vascular pathologies such as arterial aneurysma, arteriovenous malformation, stenosis, dissections or due to increased blood flow (e.g. In these cases the abnormal somatosensory neuronal input leads to abnormalities in the central auditory pathways which are then perceived as tinnitus.

Positive findings from meta-analyses are generally considered as the highest evidence for efficacy. Daily stimulation with such tailor-made music resulted in significant reduction of tinnitus loudness after one year of stimulation, as compared to a control condition (Okamoto et al.
Therefore further strategies are needed to enhance the effects in order to become relevant for clinical routine (Kleinjung & Langguth 2009). This step comprises technical tests that are tailored towards the diagnosis of specific tinnitus-related psychological (for example, depression, anxiety, insomnia) and somatic symptoms. In almost hundred chapters written by experts from many disciplines, the book aims to give an comprehensive overview of the state of the art of tinnitus management. For most of these new approaches further development is needed before they can be considered established treatments for clinical routine use. 2011, "Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation", J Neurol. Counteracting Tinnitus Symptoms And Related Pathological Cerebral Synchrony By Acoustic Coordinated Reset Neuromodulation.
2011a, "The effects of chronic tinnitus caused by acoustic trauma on social behaviour and anxiety in rats", Neuroscience, vol. This paradigm change resulted in substantial advances in the understanding of the mechanisms involved in the generation of tinnitus and its related symptoms.
The intensity of the phantom sound can vary from a subtle noise just above hearing threshold, to high intensity sounds which cannot be masked by any external noise.
Many patients with tinnitus report symptoms such as frustration, annoyance, anxiety, depression, irritation and concentration difficulties and these symptoms are highly relevant for the perceived tinnitus severity. All methods have in common that it is assumed, that animals with tinnitus do not perceive quiet periods any more.
But more work will be needed to find out whether these changes recapitulate at least to some extent the suffering of tinnitus patients.
2011) or a combination of auditory stimulation and vagal nerve stimulation (Engineer et al. For cognitive behavioural therapies two meta-analyses demonstrated beneficial effects on quality of life measures, but not on tinnitus loudness (Hesser et al. Also medications for the treatment of epilepsy have been studied in tinnitus patients, but controlled studies have not demonstrated additional benefits compared to placebo (Hoekstra et al. Once diagnosed, causally oriented treatment is recommended, but, for instances in which such treatments are unavailable or unsuccessful, symptomatic treatment options (alongside counseling) should be considered for all patients who are impaired by their tinnitus. Nevertheless the increasing understanding of the pathophysiology and the increasing number of new treatments on the horizon give rise to the hope, that soon better treatment options will become available to help the many tinnitus patients to overcome their daily suffering. 2011, "Systematic review and meta-analyses of randomized controlled trials examining tinnitus management", Laryngoscope, vol. 2011a, "Algorithm for the diagnostic and therapeutic management of tinnitus," in Textbook of Tinnitus, 1 edn, A. 2011b, "Acoustic trauma that can cause tinnitus impairs impulsive control but not performance accuracy in the 5-choice serial reaction time task in rats", Neuroscience, vol.
This deeper understanding resulted in an increasing amount of new ideas about potential treatment strategies, which are currently under development.
It has been demonstrated that all these forms differ in their brain activity pattern, especially in non-auditory brain areas. It has been a debate for many years, whether tinnitus results from the amplification of contrasts between neighboured frequencies with differences in the input.
The clinical improvement was paralleled by a reduction of tinnitus related auditory cortex evoked activity. Noteably these findings cannot yet predict whether these treatments will also work in patients with tinnitus. Also for the first time brain activity changes related to acute tinnitus after noise trauma have been studied (Ortmann et al. Findings from animal models of tinnitus clearly suggest that it is the homeostatic mechanisms, which are responsible for tinnitus generation. Thus, tinnitus which normally disappears spontaneously might persist in the presence of associated stress (De Ridder et al. In recent years a sophisticated method has been developed, that requires no training (Turner 2007): A gap in an environmental sound signals a coming loud sound. But these findings proof that the proposed treatments are in principle capable to cure tinnitus and they provide first a very promising basis for clinical studies, and second information about important details of the specific treatements.
2011) and it has been found that these differ substantially from those in chronic tinnitus. Thus in all forms of pulsatile tinnitus potential diagnostic testes should be performed to identify vascular abnormalities. An analysis of different forms of sound therapies came to the conclusion that the available studies are not sufficient to judge the efficacy of this treatment form (Hoare et al. Whereas stimulation by implanted electrodes or pharmacotherapy can be performed permanently, rTMS or tDCS can only be applied for a limited amount of time. If this “warning” gap is detected by the animal, its startle reaction to the loud sound is reduced, if not it is not reduced. Thus in summary advances in animal models in the last years have provided important contributons to a better understanding of tinnitus and are have recently become an important method in the development of new treatments. Nevertheless, these methods hold therapeutic potential since they can induce changes, which outlast the treatment period. This method has been shown in many studies to assess whether an animal perceives a phantom sound or not. Interestingly the effects of hearing aids, which are widely used in the management of tinnitus have only been very poorly investigated in the past. These long-lasting effects with limited treatment time can be either explained by learning-like effects (activation of neural plasticity) or by the disruption of dysfunctional networks, which then allow the re-establishment of a more physiological state (Langguth et al. A recent study found that only those patients benefit from hearing aids, who perceive their tinnitus below 6 kHz, which is the frequency range, in which hearing aids amplify the sound. Patients who perceive their tinnitus at higher frequencies, (where the hearing aid is not amplifying any more) do not perceive any tinnitus reduiction after hearing aid use (Schaette et al.

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