Alain Londero

Consensus for tinnitus patient assessment and treatment outcome measurement: Tinnitus Research Initiative meeting, Regensburg, July 2006.

There is widespread recognition that consistency between research centres in the ways that patients with tinnitus are assessed and outcomes following interventions are measured would facilitate more effective co-operation and more meaningful evaluations and comparisons of outcomes. At the first Tinnitus Research Initiative meeting held in Regensburg in July 2006 an attempt was made through workshops to gain a consensus both for patient assessments and for outcome measurements. It is hoped that this will contribute towards better cooperation between research centres in finding and evaluating treatments for tinnitus by allowing better comparability between studies.

Methodological aspects of clinical trials in tinnitus: A proposal for an international standard

Chronic tinnitus is a common condition with a high burden of disease. While many different treatments are used in clinical practice, the evidence for the efficacy of these treatments is low and the variance of treatment response between individuals is high. This is most likely due to the great heterogeneity of tinnitus with respect to clinical features as well as underlying pathophysiological mechanisms. There is a clear need to find effective treatment options in tinnitus, however, clinical trials differ substantially with respect to methodological quality and design. Consequently, the conclusions that can be derived from these studies are limited and jeopardize comparison between studies. Here, we discuss our view of the most important aspects of trial design in clinical studies in tinnitus and make suggestions for an international methodological standard in tinnitus trials. We hope that the proposed methodological standard will stimulate scientific discussion and will help to improve the quality of trials in tinnitus.

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.

Spontaneous and evoked otoacoustic emissions in preterm neonates

Spontaneous (SOEs) and evoked otoacoustic emissions (EOEs) were recorded in a group of preterm neonates (N = 134 ears) in order to study the basic properties of SOEs and EOEs as a function of gestational age. In the study, it was found that: 1. EOEs were recorded in 93% of the tested ears; 2. SOEs were recorded in 61% of the tested ears; 3. there were no statistically significant variations of EOE amplitude with gestational age; 4. EOE spectrum did not vary with age; and 5. the two main factors influencing EOE amplitude were the SOE presence and the fast Fourier transform spectrum, especially the lower limit of the spectrum. Thus, the maturation of outer hair cell properties appears to be complete at 32 weeks of gestational age. Because a number of infants at risk for hearing loss are preterm babies, screening for EOEs, an objective, rapid, and nontraumatic technique, may prove useful in evaluating peripheral auditory dysfunction in preterm neonates.

Transcranial magnetic stimulation (TMS) for treatment of chronic tinnitus: clinical effects.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method used to induce electrical current in the brain through impulses of strong magnetic fields applied externally. The technique can relieve tinnitus by modulating the excitability of neurons in the auditory cortex to decrease the hyperexcitability that is associated with generating the neural activity that causes some form of tinnitus. This chapter will review clinical studies using rTMS for the treatment of tinnitus.

Stimulation magnétique du cortex auditif dans les acouphènes invalidants: Résultats preliminaries

OBJECTIVE Tinnitus - the perception of sound in one or both ears or in the head when no external sound is present - can be disabling and is especially difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique for activating or inactivating specific areas of the cortex. The aim of this study was to assess the feasibility of magnetic neurostimulation of the primary and secondary auditory cortex in the treatment of disabling chronic tinnitus. PATIENTS AND METHODS Thirteen patients with tinnitus refractory to several conventional treatments underwent transcranial magnetic stimulation guided by functional magnetic resonance imaging (fMRI). We compared two types of stimulation of targets in the auditory cortex, identified by fMRI: 3-second pulses at high frequency (10 Hz) and 20-minute stimulations at a lower frequency (1 Hz). RESULTS Brief high-frequency pulses of cortical magnetic stimulation (10 Hz) were not effective. On the other hand, prolonged low frequency (1 Hz) stimulation was effective in 62.5% of patients; the effect appeared 48 h after treatment and lasted for approximately 5 days. DISCUSSION RTMS may be a new noninvasive technique for studying the cortical plasticity associated with the pathophysiologic mechanisms of chronic tinnitus and may lead to new treatment strategies for patients with disabling tinnitus resistant to all treatment.Resume Objectif Les acouphenes sont des symptomes otologiques invalidants dont le traitement est particulierement difficile. La stimulation magnetique transcrânienne repetitive (SMTr) est une technique non invasive d’activation et/ou de desactivation de zones focalisees du cortex. Le but de cette etude a ete d’apprecier la faisabilite de la neurostimulation magnetique comme test diagnostique permettant d’evaluer les possibilites de neuromodulation au niveau des cortex auditifs primaires et secondaires pour les acouphenes chroniques invalidants. Patients et methodes Treize patients ayant un acouphene refractaire aux traitements usuels ont ete selectionnes afin de beneficier d’une stimulation magnetique transcrânienne guidee par IRM fonctionnelle (IRMf). Deux types de stimulations des cibles IRMf du cortex auditif ont ete compares : des trains de 3 s a haute frequence (10 Hz) et des stimulations de 20 min a basse frequence (1 Hz). Resultats La stimulation magnetique corticale effectuee de facon breve a haute frequence (10 Hz) s’est revelee inefficace. En revanche, la stimulation prolongee a basse frequence (1 Hz) a ete efficace chez 62,5 % des patients avec un delai d’apparition de l’effet de 48 heures, et une duree moyenne de l’effet d’environ 5 jours. Discussion La SMTr pourrait etre une nouvelle technique non invasive d’etude de la plasticite corticale associee aux mecanismes physio-pathologiques du developpement d’acouphenes chroniques et permet d’envisager de nouvelles strategies therapeutiques chez des patients ayant des acouphenes invalidants et resistants a tout traitement.

Medio-Lateral Postural Instability in Subjects with Tinnitus

Background: Many patients show modulation of tinnitus by gaze, jaw or neck movements, reflecting abnormal sensorimotor integration, and interaction between various inputs. Postural control is based on multi-sensory integration (visual, vestibular, somatosensory, and oculomotor) and indeed there is now evidence that posture can also be influenced by sound. Perhaps tinnitus influences posture similarly to external sound. This study examines the quality of postural performance in quiet stance in patients with modulated tinnitus. Methods: Twenty-three patients with highly modulated tinnitus were selected in the ENT service. Twelve reported exclusively or predominately left tinnitus, eight right, and three bilateral. Eighteen control subjects were also tested. Subjects were asked to fixate a target at 40 cm for 51 s; posturography was performed with the platform (Technoconcept, 40 Hz) for both the eyes open and eyes closed conditions. Results: For both conditions, tinnitus subjects showed abnormally high lateral body sway (SDx). This was corroborated by fast Fourrier Transformation (FFTx) and wavelet analysis. For patients with left tinnitus only, medio-lateral sway increased significantly when looking away from the center. Conclusion: Similarly to external sound stimulation, tinnitus could influence lateral sway by activating attention shift, and perhaps vestibular responses. Poor integration of sensorimotor signals is another possibility. Such abnormalities would be accentuated in left tinnitus because of the importance of the right cerebral cortex in processing both auditory–tinnitus eye position and attention.

Auditory and visual 3D virtual reality therapy for chronic subjective tinnitus: theoretical framework

It is estimated that ~10% of the adult population in developed countries is affected by subjective tinnitus. Physiopathology of subjective tinnitus remains incompletely explained. Nevertheless, subjective tinnitus is thought to result from hyperactivity and neuroplastic reorganization of cortical and subcortical networks following acoustic deafferentation induced by cochlear or auditory nerve damage. Involvement of both auditory and non-auditory central nervous pathways explains the conscious perception of tinnitus and also the potentially incapacitating discomfort experienced by some patients (sound hypersensitivity, sleep disorders, attention deficit, anxiety or depression). These clinical patterns are similar to those observed in chronic pain following amputation where conditioning techniques using virtual reality have been shown both to be theoretically interesting and effectively useful. This analogy led us to develop an innovative setup with dedicated auditory and visual 3D virtual reality environments in which unilateral subjective tinnitus sufferers are given the possibility to voluntarily manipulate an auditory and visual image of their tinnitus (tinnitus avatar). By doing so, the patients will be able to transfer their subjective auditory perception to the tinnitus avatar and to gain agency on this multimodal virtual percept they hear, see and spatially control. Repeated sessions of such virtual reality immersions are then supposed to contribute to tinnitus treatment by promoting cerebral plasticity. This paper describes the theoretical framework and setup adjustments required by this very first attempt to adapt virtual reality techniques to subjective tinnitus treatment. Therapeutic usefulness will be validated by a further controlled clinical trial.

Central Crosstalk for Somatic Tinnitus: Abnormal Vergence Eye Movements

Background Frequent oulomotricity problems with orthoptic testing were reported in patients with tinnitus. This study examines with objective recordings vergence eye movements in patients with somatic tinnitus patients with ability to modify their subjective tinnitus percept by various movements, such as jaw, neck, eye movements or skin pressure. Methods Vergence eye movements were recorded with the Eyelink II video system in 15 (23–63 years) control adults and 19 (36–62 years) subjects with somatic tinnitus. Findings 1) Accuracy of divergence but not of convergence was lower in subjects with somatic tinnitus than in control subjects. 2) Vergence duration was longer and peak velocity was lower in subjects with somatic tinnitus than in control subjects. 3) The number of embedded saccades and the amplitude of saccades coinciding with the peak velocity of vergence were higher for tinnitus subjects. Yet, saccades did not increase peak velocity of vergence for tinnitus subjects, but they did so for controls. 4) In contrast, there was no significant difference of vergence latency between these two groups. Interpretation The results suggest dysfunction of vergence areas involving cortical-brainstem-cerebellar circuits. We hypothesize that central auditory dysfunction related to tinnitus percept could trigger mild cerebellar-brainstem dysfunction or that tinnitus and vergence dysfunction could both be manifestations of mild cortical-brainstem-cerebellar syndrome reflecting abnormal cross-modality interactions between vergence eye movements and auditory signals.

Eye movement abnormalities in somatic tinnitus: fixation, smooth pursuit and optokinetic nystagmus.

OBJECTIVE Smooth pursuit (SP), optokinetic nystagmus (OKN) and fixation were investigated in five subjects with somatic tinnitus modulated by eye movements, jaw or neck. METHODS Eye movements were recorded with the EyeLink II video system. RESULTS (1) Fixation was characterized by high frequency and amplitude of saccade intrusions; (2) SP had low gain particularly in the vertical direction, and it was characterized by high frequency of catch-up saccades with high amplitude, including predictive saccades; (3) OKN also had low gain particularly in the vertical direction. Each subject showed abnormality for more than one type of eye movement, and for specific directions. CONCLUSIONS AND SIGNIFICANCE The results suggest mild dysfunction of cortical-subcortical and cerebellar structures involved in the control of these eye movements. Particularly deficits for vertical pursuit eye movements and fixation instability in line with cerebellar signs. Further studies of more patients with or without modulated tinnitus are in progress.