Juergen Strutz

Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus.

OBJECTIVES: The pathophysiologic mechanisms of idiopathic tinnitus remain unclear. Recent studies demonstrated focal brain activation in the auditory cortex of patients with chronic tinnitus. Low-frequency repetitive transcranial magnetic stimulation (rTMS) is able to reduce cortical hyperexcitability. STUDY DESIGN: Fusing of the individual PET-scan with the structural MRI-scan (T1, MPRAGE) allowed us to identify exactly the area of increased metabolic activity in the auditory cortex of patients with chronic tinnitus. With the use of a neuronavigational system, this target area was exactly stimulated by the figure 8-shaped magnetic coil. In a prospective study, rTMS (110% motor threshold; 1 Hz; 2000 stimuli/day over 5 days) was performed using a placebo controlled cross-over design. Patients were blinded regarding the stimulus condition. For the sham stimulation a specific sham-coil system was used. Fourteen patients were followed for 6 months. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller). SETTING: Tertiary referral medical center. RESULTS: Increased metabolic activation in the auditory cortex was verified in all patients. After 5 days of verum rTMS, a highly significant improvement of the tinnitus score was found whereas the sham treatment did not show any significant changes. The treatment outcome after 6 months still demonstrated significant reduction of tinnitus score. CONCLUSION: These preliminary results demonstrate that neuronavigated rTMS offers new possibilities in the understanding and treatment of chronic tinnitus.

Benefits of bilateral electrical stimulation with the nucleus cochlear implant in adults: 6-month postoperative results.

Objective: To evaluate the benefits of bilateral electrical stimulation for hearing-impaired adult subjects using the Nucleus 24 cochlear implant in a multicenter study, and to compare and quantify performance on speech perception measures in quiet and in noise and localization ability for unilateral and bilateral cochlear implant use. Design: Repeated single subject measures were carried out for each subject, with each subject serving as their own control. Assessment of unilateral and bilateral listening conditions for performance on tests of speech comprehension and sound localization were performed. Speech comprehension measures were performed in quiet at 0 degree azimuth and in the presence of background noise simultaneously presented from the same speaker and spatially separated by 90 degrees, at S+45°N45° and at S−45°N+45°. Test materials included Freiburger monosyllabic words, Oldenburger sentences, and the Hochmair-Schulz-Moser sentences. Tests of localization were performed in the horizontal plane with 12 speaker locations 30 degrees apart using a shortened sentence stimulus from the Hochmair-Schulz-Moser sentences at two possible presentation levels of 55 and 70 dB sound pressure level for assessment of directionality. The binaural advantage provided by bilateral stimulation was calculated with respect to each ear separately, classified as either the better or poorer performing ear for each speech material in quiet and in noise test conditions. For localization of sound, the binaural advantage was compared with left and right ears separately. Paired comparisons for performance data in all conditions were carried out by considering measurements for each subject in different conditions as paired observations and applying the Student’s t test to determine the statistical difference between the data sets. Setting: Tertiary referral centers with a cochlear implant program. Patients: Thirty-seven profoundly hearing-impaired adults were enrolled in the study, 22 simultaneously and 15 sequentially bilaterally implanted. All patients received the Nucleus 24 cochlear implant and used the Nucleus SPrint or ESPrit 3G speech processor, with the vast majority using the ACE speech coding strategy. Results: For spatially separated speech in noise conditions, an interaural performance advantage for the ear closest to the speech source (i.e., with a superior signal to noise ratio) compared with that for the ear closest to the noise source (i.e., with an inferior signal to noise ratio) is consistently demonstrated regardless of whether it is the better or poorer performing ear closest to the speech signal. This is referred to as a significant binaural head-shadow benefit, resulting in a mean improvement between −10 dB and −11.4 dB in the critical signal to noise ratio required for 50% speech comprehension for the Olden-burger sentences and a mean improvement in the maximum score of 42% to 55% for the ear closest to the speech signal over the ear farthest away for the Hochmair-Schulz-Moser sentences. Bilateral stimulation is always observed to provide a performance advantage over the unilateral listening condition for either ear when ipsilateral to the noise source. In addition, as demonstrated by approximately half the subjects tested in noise with the Hochmair-Schulz-Moser sentences, a performance advantage of bilateral stimulation may be observed over the better ear alone when positioned ipsilateral to the speech signal, which is referred to as a binaural squelch effect. On average, for the group, this resulted in a statistically significant improvement in speech comprehension scores of 8% in the bilateral listening condition compared with the scores for the better ear alone. Through assessment of comprehension of coincidental speech in noise and speech in quiet, a significant benefit of binaural redundancy was noted for the group for Oldenburger sentence scores in noise and in quiet compared with unilateral scores for either ear and for the Freiburger monosyllabic words in quiet in comparison with the better ear alone scores. Binaural stimulation also led to a significant improvement in localization ability over either monaural condition, with the root mean square degrees of error reduced by 38 degrees compared with that observed for unilateral stimulation. Conclusion: Similar to what has been observed for bilateral acoustic stimulation in the past, bilateral electrical stimulation provides the foundation for the potential advantages of the head-shadow effect, providing a binaural head-shadow benefit and binaural auditory processing such as binaural redundancy and binaural squelch effects, all of which combine to lead to improved speech comprehension over unilateral listening conditions. The combination of improved speech comprehension and improved localization ability made available through bilateral electrical stimulation provides the necessary foundation to further assist the hearing-impaired listener to better cope with communication in the everyday listening situation both in noise and in quiet.

Combined temporal and prefrontal transcranial magnetic stimulation for tinnitus treatment: a pilot study.

Objectives Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been proposed as a new treatment strategy for patients with chronic tinnitus. However, functional abnormalities in tinnitus patients also involve brain structures used for attentional and emotional processing, such as the dorsolateral prefrontal cortex. Therefore, we have developed a new rTMS treatment strategy for tinnitus patients that consists of a combination of high-frequency prefrontal and low-frequency temporal rTMS. Study Design A total of 32 patients received either low-frequency temporal rTMS or a combination of high-frequency prefrontal and low-frequency temporal rTMS. Treatment effects were assessed with a standardized tinnitus questionnaire (TQ). Results Directly after therapy there was an improvement of the TQ-score for both groups, but no differences between groups. An evaluation after 3 months revealed a remarkable benefit from the use of combined prefrontal and temporal rTMS treatment. Conclusion These results support recent data that suggest that auditory and nonauditory brain areas are involved in tinnitus pathophysiology.

Curing tinnitus with a Cochlear Implant in a patient with unilateral sudden deafness: a case report

Cochlear implantation is a routine procedure for patients with bilateral profound sensorineural hearing loss. Some reports demonstrated a suppression of tinnitus as a side-effect after implantation. We describe the case of a 55-year-old man suffering from severe right-sided tinnitus in consequence of sudden right-sided deafness. Multiple therapeutic efforts including intravenous steroids and tympanoscopy with grafting of the round window remained unsuccessful. One year after onset of symptoms right-sided cochlear implantation was performed, which resulted in a complete abolishment of tinnitus after activating the implant. Severe unilateral tinnitus after sudden deafness might represent a new indication for cochlear implantation.

Levodopa does not enhance the effect of low-frequency repetitive transcranial magnetic stimulation in tinnitus treatment

OBJECTIVE: Low-frequency repetitive transcranial magnetic stimulation (rTMS) has shown promise for the treatment of tinnitus. Experimental data from motor cortex stimulation in healthy subjects indicate that the suppressing effect of low-frequency rTMS can be enhanced by dopaminergic receptor activation. Here we investigated whether administration of the dopamine precursor levodopa before low-frequency rTMS enhances its efficacy in tinnitus treatment. STUDY DESIGN: Sixteen patients with chronic tinnitus received 100 mg of levodopa before each session of low-frequency rTMS. Results were compared with a matched control group of 16 patients who received the same treatment, but without levodopa. Treatment outcome was assessed with a standardized tinnitus questionnaire. RESULTS: Both stimulation protocols resulted in a significant reduction of tinnitus scores after 10 days of stimulation; however, there was no significant difference between the two groups. CONCLUSION: Our data suggest that 100 mg of levodopa does not enhance the effect of rTMS in the treatment of tinnitus.

Repetitive transcranial magnetic stimulation for tinnitus treatment: No enhancement by the dopamine and noradrenaline reuptake inhibitor bupropion

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has shown beneficial effects in patients with chronic tinnitus. Recent preclinical data in healthy controls suggest that the effects of low-frequency rTMS can be enhanced by dopaminergic drugs. OBJECTIVE We investigated whether application of the dopamine reuptake inhibitor bupropion increases the clinical effects of low-frequency rTMS over the auditory cortex in tinnitus patients. SUBJECTS AND METHODS Eighteen subjects with chronic tinnitus received 10 sessions of 1 Hz rTMS (2000 pulses/day, 110% motor threshold) applied to the left temporal cortex. In addition, these subjects received one dosage of 150 mg bupropion (Wellbutrin XL/Elontril) 4 hours before each TMS session. Treatment outcome was assessed with a tinnitus questionnaire over a 3-month period. Treatment effects were compared with a control group of 100 tinnitus patients matched for age, tinnitus duration, and tinnitus questionnaire baseline scores, who received the same rTMS treatment without prior bupropion application. RESULTS For the whole sample, there was a significant effect of rTMS treatment over time. There were no significant differences between the bupropion and the control group. CONCLUSIONS Our data suggest that 150 mg bupropion administration does not enhance the effect of rTMS in the treatment of tinnitus.

Effects of Botulinum Toxin A on Cytokine Synthesis in a Cell Culture Model of Cutaneous Scarring

OBJECTIVE To evaluate possible botulinum toxin A effects in a cell culture model. METHODS In a cell culture model with dermal fibroblasts and microvascular endothelial cells, possible botulinum toxin A effects were evaluated. Cell proliferation and cytokine expression were analyzed using viability assays and enzyme-linked immunosorbent assay techniques. RESULTS Neither cell proliferation nor cytokines and growth factors (interleukin 6, monocyte chemoattractant protein 2, fibroblast growth factor, macrophage colony-stimulating factor, and vascular endothelial growth factor) were affected by botulinum toxin A incubation. CONCLUSIONS The present data do not add evidence to suggest a significant therapeutic role of botulinum toxin A injections for cutaneous wound healing beyond chemoimmobilization. Further studies that include patient-specific cells of hypertrophic scars are required to better understand what role botulinum toxin A can play in the treatment of mature scar tissue.

The Relevance of the High Frequency Audiometry in Tinnitus Patients with Normal Hearing in Conventional Pure-Tone Audiometry

Objective. The majority of tinnitus patients suffer from hearing loss. But a subgroup of tinnitus patients show normal hearing thresholds in the conventional pure-tone audiometry (125 Hz–8 kHz). Here we explored whether the results of the high frequency audiometry (>8 kHz) provide relevant additional information in tinnitus patients with normal conventional audiometry by comparing those with normal and pathological high frequency audiometry with respect to their demographic and clinical characteristics. Subjects and Methods. From the database of the Tinnitus Clinic at Regensburg we identified 75 patients with normal hearing thresholds in the conventional pure-tone audiometry. We contrasted these patients with normal and pathological high-frequency audiogram and compared them with respect to gender, age, tinnitus severity, pitch, laterality and duration, comorbid symptoms and triggers for tinnitus onset. Results. Patients with pathological high frequency audiometry were significantly older and had higher scores on the tinnitus questionnaires in comparison to patients with normal high frequency audiometry. Furthermore, there was an association of high frequency audiometry with the laterality of tinnitus. Conclusion. In tinnitus patients with normal pure-tone audiometry the high frequency audiometry provides useful additional information. The association between tinnitus laterality and asymmetry of the high frequency audiometry suggests a potential causal role for the high frequency hearing loss in tinnitus etiopathogenesis.

Transcranial magnetic stimulation for the treatment of tinnitus

Wir freuen uns, dass unsere Pilotstudie zur Behandlung von Tinnitus mit transkranieller Magnetstimulation (TMS) so große Aufmerksamkeit findet und möchten Herrn Dr. Hesse für seinen Beitrag danken. Wir stimmen Herrn Dr. Hesse vorbehaltlos in der Aussage zu, dass die momentane Studienlage noch keine abschließende Beurteilung der Wirksamkeit der TMS zur Tinnitusbehandlung zulässt. Dies ist von uns auch wiederholt zum Ausdruck gebracht worden [18, 12]. Der Beitrag zeigt uns jedoch, dass auch bei Kollegen, die sich sehr intensiv mit diesem Thema beschäftigen, erhebliche Verständnisschwierigkeiten bestehen. Ein großer Teil dieser Missverständnisse scheint dadurch bedingt zu sein, dass verschiedene Anwendungsformen der TMS nicht ausreichend differenziert betrachtet werden. Grundsätzlich ist zu bemerken, dass es sich bei der TMS um eine Methode handelt, die als diagnostisches, als neurowissenschaftliches und als therapeutisches Instrument eingesetzt werden kann. Bei Anwendung als repetitive TMS (rTMS; darunter versteht man die rhythmische Wiederholung einzelner Stimuli) können direkt stimulierte Gehirnareale sowie entfernte, mit dem stimulierten Areal funktionell verbundene Gehirnstrukturen in ihrer Aktivität moduliert werden [19]. Dabei ist der neurobiologische Effekt der rTMS entscheidend von den verwendeten Stimulationsparametern abhängig. Als besonders bedeutsamer Stimulationsparameter hat sich die Stimulationsfrequenz erwiesen. Weiter wurde gezeigt, dass rTMS bei wiederholter Anwendung über mehrere Tage hinweg in der Lage ist, neuroplastische Umbauvorgänge zu induzieren, die therapeutisch genutzt werden können [5, 15]. Dementsprechend müssen die vorliegenden Studien differenzierter betrachtet werden. Der Effekt einer einmaligen hochfrequenten rTMS über dem temporalen Kortex wurde in mehreren Studien untersucht [17, 2, 14, 4]. Richtig gestellt werden sollte in diesem Zusammenhang, dass die letztere Arbeit mit 15 Patienten die Einzige ist, die die Arbeitsgruppe um Robert Folmer und William Martin aus Portland durchgeführt hat (pers. Mitteilung). Die Behauptung von Herrn Dr. Hesse, dass von dieser Gruppe eine Studie mit 100 Patienten und negativen Ergebnissen durchgeführt worden sei, ist nicht richtig. Insgesamt zeigte sich bei diesen Studien als relativ robustes Ergebnis, dass es bei einem Teil der untersuchten Patienten nach einer einmaligen hochfrequenten rTMS-Applikation über dem temporalen Kortex zu einer passageren Verminderung der Tinnituswahrnehmung kam, die meist nur Minuten andauerte. Sofern in den Studien statistische Berechnungen durchgeführt wurden, war dieser Effekt im Vergleich zu einer Placebobedingung signifikant. Diese Ergebnisse deuten klar darauf hin, dass rTMS über dem temporalen Kortex Funktionsveränderungen in Gehirnarealen induzieren kann, die mit der Tinnituswahrnehmung in Zusammenhang stehen. In einer dieser Studien wurde der Effekt einer einmaligen hochfrequenten und niedrigfrequenten Applikation verglichen. Dabei zeigten sich nach niedrigfrequenter Anwendung wesentlich länger andauernde Effekte als nach hochfrequenter Stimulation [14]. Basierend auf umfangreicher präklinischer und klinischer Studienlage zum Einsatz niedrigfrequenter rTMS bei Erkrankungen, die mit fokaler Hyperexzitabilität einhergehen [5], untersuchten wir in der von Herrn Dr. Hesse kommentierten placebokontrollierten Studie [7] den Effekt einer 5-tägigen niedrigfrequenten rTMS-Behandlung. Nach Ansicht von Herrn Dr. Hesse weist diese Studie mehrere Schwachstellen auf, auf die wir gern im Detail eingehen möchten. Zunächst wird die Bedeutung der mit funktionell bildgebenden Methoden dargestellten Hyperaktivität im auditorischen Kortex angezweifelt. Sicherlich ist richtig, dass mit Tinnitus assoziierte Veränderungen im Zentralnervensystem nicht auf das auditorische System beschränkt sind [11]. Die Bedeutung des auditorischen Kortex für die Pathophysiologie des chronischen Tinnitus wird jedoch durch vielfältige neurowisssenschaftliche Studien gestützt [1, 16, 20]. Auch kann die Annahme, dass dem auditorischen Kortex bei der bewussten Wahrnehmung eines auKommentar zum Beitrag

Influence of Surface Processing on the Biocompatibility of Titanium

Surface conditioning of titanium middle ear implants results in an improved biocompatibility, which can be characterized by the properties of fibroblasts cultured on conditioned surfaces. Titanium has been established as a favorable biomaterial in ossicular chain reconstruction. The epithelization of the surface of the implants is important for their integration and stable positioning in the middle ear. Mouse fibroblast cells were cultured on platelets made from pure Grade 2 titanium. Platelets that had been etched along their production process were compared to unetched platelets. The DNA in the cell nuclei was stained with DAPI and the actin filaments of the cytoskeleton were stained with FITC-conjugated phalloidin in order to analyze the cells grown on etched and unetched platelets by fluorescence microscopy. SEM (scanning electron microscopic) images were used to compare the surface structure of etched and unetched titanium platelets. There was a statistically significant increase of the area covered by the cytoplasm and increased actin expression by fibroblasts grown on the etched titanium platelets. In addition, the area of the platelets covered by nuclei on the etched platelets exceeded on average the one on unetched platelets, although this difference was not significant. The SEM pictures comparing unetched and etched titanium platelets showed a clear difference in surface structure. Surface conditioning of titanium implants improved the epithelization by fibroblasts and consequently etched titanium should be the preferred biomaterial for reconstructive middle ear surgery.