Tinnitus and tinnitus disorder: Theoretical and operational definitions (an international multidisciplinary proposal).

As for hypertension, chronic pain, epilepsy and other disorders with particular symptoms, a commonly accepted and unambiguous definition provides a common ground for researchers and clinicians to study and treat the problem. The WHO's ICD11 definition only mentions tinnitus as a nonspecific symptom of a hearing disorder, but not as a clinical entity in its own right, and the American Psychiatric Association's DSM-V doesn't mention tinnitus at all. Here we propose that the tinnitus without and with associated suffering should be differentiated by distinct terms: "Tinnitus" for the former and "Tinnitus Disorder" for the latter. The proposed definition then becomes "Tinnitus is the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source, which becomes Tinnitus Disorder "when associated with emotional distress, cognitive dysfunction, and/or autonomic arousal, leading to behavioural changes and functional disability.". In other words "Tinnitus" describes the auditory or sensory component, whereas "Tinnitus Disorder" reflects the auditory component and the associated suffering. Whereas acute tinnitus may be a symptom secondary to a trauma or disease, chronic tinnitus may be considered a primary disorder in its own right. If adopted, this will advance the recognition of tinnitus disorder as a primary health condition in its own right. The capacity to measure the incidence, prevalence, and impact will help in identification of human, financial, and educational needs required to address acute tinnitus as a symptom but chronic tinnitus as a disorder.

Sensorineural Tinnitus: Its Pathology and Probable Therapies.

Tinnitus is not a single disease but a group of different diseases with different pathologies and therefore different treatments. Regarding tinnitus as a single disease is hampering progress in understanding of the pathophysiology of tinnitus and perhaps, more importantly, it is a serious obstacle in development of effective treatments for tinnitus. Subjective tinnitus is a phantom sound that takes many different forms and has similarities with chronic neuropathic pain. The pathology may be in the cochlea, in the auditory nerve, or, most commonly, in the brain. Like chronic neuropathic pain tinnitus is not life threatening but influences many normal functions such as sleep and the ability to concentrate on work. Some forms of chronic tinnitus have two components, a (phantom) sound and a component that may best be described as suffering or distress. The pathology of these two components may be different and the treatment that is most effective may be different for these two components. The most common form of treatment of tinnitus is pharmacological agents and behavioral treatment combined with sound therapy. Less common treatments are hypnosis and acupuncture. Various forms of neuromodulation are becoming in use in an attempt to reverse maladaptive plastic changes in the brain.

Directing neural plasticity to understand and treat tinnitus.

The functional organization of cortical and subcortical networks can be altered by sensory experience. Sensory deprivation destabilizes neural networks resulting in increased excitability, greater neural synchronization and increased spontaneous firing in cortical and subcortical neurons. This pathological activity is thought to generate the phantom percept of chronic tinnitus. While sound masking, pharmacotherapy and cortical stimulation can temporarily suppress tinnitus for some patients, these interventions do not eliminate the pathological activity that is responsible for tinnitus. A treatment that could reverse the underlying pathology would be expected to be effective in alleviating the symptoms, if not curative. Targeted neural plasticity can provide the specificity required to restore normal neural activity in dysfunctional neural circuits that are assumed to underlie many forms of tinnitus. The forebrain cholinergic system and the noradrenergic system play a significant role in modulating cortical plasticity. Stimulation of the vagus nerve is known to activate these neuromodulatory pathways. Our earlier studies have demonstrated that pairing sounds with either nucleus basalis of Meynert (NB) stimulation or vagus nerve stimulation (VNS) generates highly specific and long-lasting plasticity in auditory cortex neurons. Repeatedly pairing tones with brief pulses of VNS reversed the physiological and behavioral correlates of tinnitus in noise exposed rats. We also recently demonstrated that VNS modulates synchrony and excitability in the auditory cortex at least in part by activation of muscarinic acetylcholine receptors, suggesting that acetylcholine is involved in the mechanism of action of VNS. These results suggest that pairing sounds with VNS provides a new avenue of treatment for some forms of tinnitus. This paper discusses neuromodulation as treatment for tinnitus with a focus on the potential value of pairing VNS with sound stimulation as a treatment of chronic tinnitus.

Vascular compression of the cochlear nerve and tinnitus: a pathophysiological investigation.

OBJECTIVE: Chronic microvascular compressions of the eighth nerve induce a slowing down of signal transmission in the auditory nerve, electrophysiologically characterized by IPL I-III prolongation. METHODS: The authors hypothesize this is compensated by an active slowing down of signal transmission of the contralateral input at the level of the brainstem, characterized by contralateral IPL III-V prolongation. RESULTS: Differences between ipsilateral and contralateral IPL I-III and IPL III-V are analyzed before and after microvascular decompression. ABR diagnostic criteria for microvascular compression are ipsilateral IPL I-III prolongation or ipsilateral peak II decrease + ipsilateral IPL I-III prolongation. With IPL I-III as diagnostic criterion, unlike preoperatively the difference between the ipsi- and contralateral IPL I-III is significant postoperatively. When using the stricter diagnostic criterion of IPL I-III + peak II, there is a preoperative significant difference between ipsi- and contralateral IPL I-III, but postoperatively the difference between the ipsi- and contralateral IPL I-III is not significant. CONCLUSIONS: Preoperatively, there is a marginal significant difference between the ipsi- and contralateral IPL III-V, which disappears postoperatively.

Techniques of intraoperative monitoring for spinal cord function: their past, present, and future directions.

PURPOSE: The authors discuss the use of intraoperative monitoring of spinal cord function as an essential part of operations in which the spinal cord is at risk. Although early documented cases of intraoperative monitoring were during operations to correct spinal deformities such as scoliosis, intraoperative monitoring has also increased safety during other operations, such as tumor resection and arteriovenous malformation ablation. METHODS: The authors highlight details involved in monitoring spinal cord function intraoperatively and discuss historical, current, and future perspectives on the use of these monitoring techniques as an essential part of operations in which the spinal cord is at risk. RESULTS: Intraoperative monitoring techniques mitigate the risk of post-operative deficits to the spinal cord by detecting injuries before they become permanent and while they can be reversed. CONCLUSIONS: Intraoperative spinal cord monitoring is safe, cost-effective, and valuable in reducing post-operative sensory and motor deficit. This technique should continue to be refined and its use consistently applied in any procedure where injury to the spinal cord is possible.

Transcranial magnetic stimulation and extradural electrodes implanted on secondary auditory cortex for tinnitus suppression.

OBJECT: Tinnitus is a prevalent symptom, with clinical, pathophysiological, and treatment features analogous to pain. Noninvasive transcranial magnetic stimulation (TMS) and intracranial auditory cortex stimulation (ACS) via implanted electrodes into the primary or overlying the secondary auditory cortex have been developed to treat severe cases of intractable tinnitus. METHODS: A series of 43 patients who benefited transiently from 2 separate placebo-controlled TMS sessions underwent implantation of auditory cortex electrodes. Targeting was based on blood oxygen level-dependent activation evoked by tinnitus-matched sound, using functional MR imaging-guided neuronavigation. RESULTS: Thirty-seven percent of the patients responded to ACS with tonic stimulation. Of the 63% who were nonresponders, half benefited from burst stimulation. In total, 33% remained unaffected by the ACS. The average tinnitus reduction was 53% for the entire group. Burst stimulation was capable of suppressing tinnitus in more patients and was better than tonic stimulation, especially for noise-like tinnitus. For pure tone tinnitus, there were no differences between the 2 stimulation designs. The average pure tone tinnitus improvement was 71% versus 37% for noise-like tinnitus and 29% for a combination of both pure tone and noise-like tinnitus. Transcranial magnetic stimulation did not predict response to ACS, but in ACS responders, a correlation (r = 0.38) between the amount of TMS and ACS existed. A patient's sex, age, or tinnitus duration did not influence treatment outcome. CONCLUSIONS: Intracranial ACS might become a valuable treatment option for severe intractable tinnitus. Better understanding of the pathophysiological mechanisms of tinnitus, predictive functional imaging tests, new stimulation designs, and other stimulation targets are needed to improve ACS results.

Hemilingual spasm: defining a new entity, its electrophysiological correlates and surgical treatment through microvascular decompression.

OBJECTIVE: We report on vascular compression syndrome of the 12th cranial nerve (hypoglossal), an occurrence not previously reported, and demonstrate, through corresponding objective electrophysiological evidence, that microvascular decompression of the hypoglossal nerve root can cure hemilingual spasm. CLINICAL PRESENTATION: A 52-year-old man had lower face muscle twitching and tongue spasms, which worsened with talking, chewing, or emotional stress. Carbamazepine offered only temporary relief, and relief from injections of botulinum toxin was insignificant. He was referred for surgical treatment. High-resolution magnetic resonance imaging of his posterior fossa contents revealed no obvious evidence of any compressive vessel along the facial nerve, but a compressive vessel along the hypoglossal nerve was apparent. INTERVENTION: The presence of preoperative tongue spasms encouraged interoperative monitoring of tongue motor responses. The facial nerve exit zone was explored, but microsurgical inspection of the seventh/eighth cranial nerve complex did not reveal any compressive vessel. However, at the anterolateral aspect of the medulla oblongata, the hypoglossal nerve was clearly compressed and distorted laterally by a large tortuous vertebral artery. When the artery was mobilized away from the nerve, the abnormal late electromyographic response to transcranial electrical stimulation disappeared; immediately after shredded Teflon was interpositioned between the artery and the nerve, the abnormal spontaneous tongue fasciculation also disappeared. The patient has remained spasm free 6 months after surgery. CONCLUSION: Hemilingual spasm may be caused by vascular contact/compression along cranial nerve XII at the lower brainstem and belong to the same family of cranial nerve hyperactivity disorders as hemifacial spasm.

Microvascular decompression for tinnitus: significant improvement for tinnitus intensity without improvement for distress. A 4-year limit.

OBJECTIVE: Microvascular compressions of the cochlear nerve can lead to tinnitus. The tinnitus initially is related to nonsynchronous signal transmission in the auditory nerve, neurophysiologically characterized by a peak II amplitude decrease. Chronic compression can lead to a focal demyelination, resulting in an increase in Iinterpeak latency I-III with tinnitus and frequency-specific hearing loss as a consequence. Decompressing the cochlear nerve may result in improvement in tinnitus if the auditory nerve is not too damaged for recovery. The aim of the study is to find a cut-off point for this recovery based on clinical data. MATERIALS AND METHODS: Twenty patients undergo a microvascular decompression of the vestibulocochlear nerve for unilateral intractable tinnitus. Pre- and postoperative visual analogue scale for tinnitus intensity and tinnitus questionnaires for tinnitus distress are analyzed before and after microvascular decompression. RESULTS: Of the 20 patients studied, 10 had improvements on their tinnitus visual analogue score intensity postoperatively, 8 were unchanged, and 2 worsened. On the Tinnitus Questionnaire scores, 7 of 13 patients improved and 6 of the 13 patients worsened. If decompression is performed before the end of the 4th year of tinnitus duration, a significant tinnitus intensity improvement can be obtained (P < .05); after 4 years, improvement cannot be obtained (P = .55). However, the tinnitus distress does not seem to decrease significantly. CONCLUSION: Microvascular decompression of the cochlear nerve can improve tinnitus intensity in selected patients if decompression is performed early, before the end of the 4th year. Tinnitus distress does not seem to change.

Plasticity diseases.

OBJECTIVE: The aim of this paper is to review the effects of activation of neural plasticity and present hypotheses using a systems approach about how activation of neural plasticity can cause symptoms and signs of disease (plasticity diseases). METHODS: Literature review. RESULTS: It is hypothesized that a program that is initiated by internal or external events controls plastic changes in specific structures of the CNS. Not all structures that have abnormal activity are pathologic but some behave pathological because they receive abnormal input from pathologic structures. The changes in function may remain after the events that elicited the expression of neural plasticity no longer exist. CONCLUSION: Activation of neural plasticity can have beneficial effects and it can cause symptoms and signs of disease. Activation of neural plasticity can help to adapt to changing demands and it is necessary for normal childhood development of the central nervous system. Plastic changes can cause signs and symptoms of disease by abnormal neural activity in pathologic structures and in structures that receive input from pathologic structures. It is hypothesized that a program controls the plastic changes and that failure in activation of neural plasticity can cause developmental disorders such as autism.

Hemilingual spasm: pathophysiology.

In the present offering, the authors provide evidence for the role of the hypoglossal motonucleus in causing a cranial nerve hyperactivity syndrome, namely hemilingual spasm. During a microvascular decompression operation to treat hemilingual spasm, transcranial stimulation elicited a delayed electromyographic (EMG) response from the tongue. This late volley of EMG activity occurred with a latency of approximately 40 ms, lasted approximately 50 ms, and disappeared when the offending vessel was displaced away from the exit zone of the hypoglossal nerve root along medulla oblongata. This late tongue EMG response resembles those found in facial muscles of the patients with hemifacial spasm (HFS). In HFS, electrical stimulation of a branch of facial nerve may elicit an EMG response with a latency of approximately 10 ms in muscles innervated by another branch of the nerve, followed by a variable volley of EMG activity that may last 100 ms or longer. This abnormal response, known as the lateral spread response, is a characteristic sign for hemifacial spasm that disappears after the offending vessel is moved off the facial nerve root. The results of the present study indicate that the EMG signs of hemilingual spasm are similar to those of HFS and that the tongue spasms are most likely caused by hyperactivity of the hypoglossal motonucleus. Based on the authors' knowledge, the above detailed electrophysiological findings related to hemilingual spasm have not been previously reported in the literature.

Controversy: Does repetitive transcranial magnetic stimulation/ transcranial direct current stimulation show efficacy in treating tinnitus patients?

BACKGROUND: Tinnitus affects 10% of the population, its pathophysiology remains incompletely understood, and treatment is elusive. Functional imaging has demonstrated a relationship between the intensity of tinnitus and the degree of reorganization in the auditory cortex. Experimental studies have further shown that tinnitus is associated with synchronized hyperactivity in the auditory cortex. Therefore, targeted modulation of auditory cortex has been proposed as a new therapeutic approach for chronic tinnitus. METHODS: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive methods that can modulate cortical activity. These techniques have been applied in different ways in patients with chronic tinnitus. Single sessions of high-frequency rTMS over the temporal cortex have been successful in reducing the intensity of tinnitus during the time of stimulation and could be predictive for treatment outcome of chronic epidural stimulation using implanted electrodes. RESULTS: Another approach that uses rTMS as a treatment for tinnitus is application of low-frequency rTMS in repeated sessions, to induce a lasting change of neuronal activity in the auditory cortex beyond the duration of stimulation. Beneficial effects of this treatment have been consistently demonstrated in several small controlled studies. However, results are characterized by high interindividual variability and only a moderate decrease of the tinnitus. The role of patient-related (for example, hearing loss, tinnitus duration, age) and stimulation-related (for example, stimulation site, stimulation protocols) factors still remains to be elucidated. CONCLUSIONS: Even in this early stage of investigation, there is a convincing body of evidence that rTMS represents a promising tool for pathophysiological assessment and therapeutic management of tinnitus. Further development of this technique will depend on a more detailed understanding of the neurobiological effects mediating the benefit of TMS on tinnitus perception. Moreover clinical studies with larger sample sizes and longer follow-up periods are needed.

Tinnitus: presence and future.

Tinnitus has many forms; it can be caused by sounds generated in the body (objective tinnitus) that reaches the ear through conduction in body tissue, but much more common is the tinnitus that occurs without any physical sound reaching the ear. Such tinnitus (subjective tinnitus) is a phantom sensation, where abnormal neural activity is generated in the ear, the auditory nerve, or the central nervous system. There are many forms of subjective tinnitus and it can occur with different severity. Subjective tinnitus often occurs in connection with hearing loss such as may occur after exposure to loud sounds (noise), or after administration of drugs such as certain antibiotics, but often no cause can be found. Tinnitus often occurs together with presbycusis and it can occur in deafness. Tinnitus is a part of the symptoms of Ménière's disease and individuals with vestibular Schwannoma almost always have tinnitus. Some individuals who have severe tinnitus hear sounds as distorted and some have hyperacusis (reduced tolerance to sounds) or phonophobia (fear of sounds). Tinnitus can be referred to one ear, or both ears, or to a location inside the head. The anatomical location of the physiological abnormality of chronic subjective tinnitus, however, is rarely in the ear but more often in the auditory nervous system. There are indications that the pathophysiology of unilateral and bilateral tinnitus is different. There is considerable evidence that expression of neural plasticity plays a central role in the development of the abnormalities that cause many forms of chronic subjective tinnitus. Expression of neural plasticity can change the balance between excitation and inhibition in the nervous system, promote hyperactivity, and it can cause reorganization of specific parts of the nervous system or redirection of information to parts of the nervous system not normally involved in processing of sounds (non-classical or extralemniscal pathways). Since there are many kinds of subjective tinnitus, search for a (single) cure for tinnitus is futile. Testing of new treatments is hampered by the fact that it is not possible to distinguish between different forms of tinnitus for which different treatments may be effective.

The role of neural plasticity in tinnitus.

There is considerable evidence that expression of neural plasticity plays a central role in the development of the abnormalities that cause many forms of tinnitus. Expression of neural plasticity can change the balance between excitation and inhibition, promote hyperactivity, and cause re-organization of specific parts of the nervous system or redirection of information to parts of the nervous system not normally involved in processing of sounds (such as the non-classical, or extralemniscal pathways). The strongest promoter of expression of neural plasticity is deprivation of input, which explains why tinnitus often occurs together with hearing loss or injury to the auditory nerve.

Microvascular decompression operations.

Moving a blood vessel off the intracranial portion of the auditory nerve can successfully cure some individuals with specific forms of subjective tinnitus. This operation, known as microvascular decompression (MVD) is in general use to treat other hyperactive disorders such as hemifacial spasm (HFS) and trigeminal neuralgia (TGN) where the operation has a success rate of approximately 85%. MVD for tinnitus has lower success rate. MVD operations have also been used to treat some forms of vestibular disorders, disabling positional vertigo (DPV). In a study of treatment of a selected group of 72 patients with severe tinnitus and signs of change in the conduction properties of the auditory nerve 13 (18.2%) had total relief from tinnitus after MVD, 16 (22.2%) had marked improvement, 8 slight improvement and 33 (45.8%) no improvement. Two patients became worse (2.8%). There were 40 men and 32 women in the study group and there was considerable difference in the success rate for men and women. Fifty-five percent of the women and 29% of men showed relief or improvement. The success of the operation depended on the length of time the participants in the study had had their tinnitus and it was best for those who had had tinnitus for less than 3 years. The success rate for bilateral tinnitus was much lower than for unilateral tinnitus.

Theta, alpha and beta burst transcranial magnetic stimulation: brain modulation in tinnitus.

INTRODUCTION: Some forms of tinnitus are considered to be auditory phantom phenomena related to reorganization and hyperactivity of the auditory central nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool capable of modulating human brain activity, using single pulse or burst stimuli. Burst rTMS has only been performed in the theta range, and has not been used clinically. The authors analyze whether burst TMS at theta (5 Hz), alpha (10 Hz) and beta (20 Hz) frequencies can temporarily suppress narrow band noise/white noise tinnitus, which has been demonstrated to be intractable to tonic stimulation. METHODS: rTMS is performed both in tonic and burst mode in 46 patients contralateral to the tinnitus side, at 5, 10 and 20 Hz. Fourteen placebo negative rTMS responders are further analyzed. RESULTS: In 5 patients, maximal tinnitus suppression is obtained with theta, in 2 with alpha and in 7 with beta burst stimulation. Burst rTMS suppresses narrow band/white tinnitus much better than tonic rTMS t(13)=6.4, p<.000. Women experience greater suppression of their tinnitus with burst stimulation than men, t(12)=2.9, p<.05. Furthermore left sided tinnitus is perceived as more distressing on the TQ than right sided tinnitus, t(12)=3.2, p<.01. The lower the tinnitus pitch the more effectively rTMS suppresses tinnitus(r=-0.65, p<0.05). DISCUSSION: Burst rTMS can be used clinically, not only theta burst, but also alpha and beta burst. Burst rTMS is capable of suppressing narrow band/white noise tinnitus very much better than tonic rTMS. This could be due the simple fact that burst neuromodulation is more powerful than tonic neuromodulation or to a differential effect of burst and tonic stimulation on the lemniscal and extralemniscal auditory system. In some patients only alpha or beta burst rTMS is capable of suppressing tinnitus, and theta burst not. Therefore in future rTMS studies it could be worthwhile not to limit burst stimulation to theta burst rTMS.

Do tonic and burst TMS modulate the lemniscal and extralemniscal system differentially?

INTRODUCTION: Tinnitus is an auditory phantom percept related to tonic and burst hyperactivity of the auditory system. Two parallel pathways supply auditory information to the cerebral cortex: the tonotopically organised lemniscal system, and the non-tonotopic extralemniscal system, firing in tonic mode and burst mode respectively. Transcranial magnetic stimulation (TMS) is a non-invasive method capable of modulating activity of the human cortex, by delivering tonic or burst stimuli. Burst stimulation is shown to be more powerful in activating the cerebral cortex than tonic stimulation and bursts may activate neurons that are not activated by tonic stimulations. METHODS: The effect of both tonic and burst TMS in 14 placebo-negative patients presenting narrow band/white noise tinnitus were analysed. RESULTS: Our TMS results show that narrow band/white noise tinnitus is better suppressed with burst TMS in comparison to tonic TMS, t(13)=6.4, p=.000. For pure tone tinnitus no difference is found between burst or tonic TMS, t(13)=.3, ns. DISCUSSION: Based on the hypothesis that white noise is the result of hyperactivity in the non-tonotopic system and pure tone tinnitus of the tonotopic system, we suggest that burst stimulation modulates the extralemniscal system and lemniscal system and tonic stimulation only the lemniscal system.

Neural plasticity in tinnitus.

Two distinctly different kinds of tinnitus occur: objective and subjective tinnitus. Objective tinnitus is caused by sounds generated in the body while subjective tinnitus is caused by abnormal neural activity that is not evoked by sound. This chapter discusses subjective tinnitus. Subjective tinnitus has many forms. In most forms of tinnitus the anatomical location of the physiological abnormality is in the central nervous system, although the sensation is often referred to one ear or both ears. The cause of most forms of subjective tinnitus is the changes that have occurred as a result of expression of neural plasticity, thus a form of reprogramming of the brain that is not to the benefit of the individual person. Tinnitus often occurs together with hearing loss, indicating that the expression of neural plasticity has been evoked by deprivation of input. Tinnitus is often accompanied by hyperacusis, and sometimes phonophobia and depression, indicating altered processing of auditory information or rerouting of information. Several studies have brought evidence that some forms of tinnitus are associated with an abnormal involvement of the nonclassical (extralemniscal, diffuse, or polysensory) auditory pathways that bypass the primary auditory cerebral cortex and provide subcortical connections to limbic structures among others. There is no general treatment for tinnitus, but there are several treatments that can alleviate or reduce the tinnitus in some patients.

History of cochlear implants and auditory brainstem implants.

Cochlear implants have evolved during the past 30 years from the single-electrode device introduced by Dr. William House, to the multi-electrode devices with complex digital signal processing that are in use now. This paper describes the history of the development of cochlear implants and auditory brainstem implants (ABIs). The designs of modern cochlear and auditory brainstem implants are described, and the different strategies of signal processing that are in use in these devices are discussed. The primary purpose of cochlear implants was to provide sound awareness in deaf individuals. Modern cochlear implants provide much more, including good speech comprehension, and even allow conversing on the telephone. ABIs that stimulate the cochlear nucleus were originally used only in patients with neurofibromatosis type 2 who had lost hearing due to removal of bilateral vestibular schwannoma. In such patients, ABIs provided sound awareness and some discrimination of speech. Recently, similar degrees of speech discrimination as achieved with cochlear implants have been obtained when ABIs were used in patients who had lost function of their auditory nerve on both sides for other reasons such as trauma and atresia of the internal auditory meatus.