Change in EEG Activity is Associated with a Decrease in Tinnitus Awareness after rTMS.

OBJECTIVE: To examine how 1Hz and 10Hz rTMS temporarily influence ratings of tinnitus loudness, annoyance, and awareness. The thalamocortical dysrhythmia (TCD) model of tinnitus was tested by examining changes in spectral power and coherence of resting state EEGs from baseline to each phase of treatment and correlating these data with change in tinnitus. METHODS: Nineteen participants completed a double-blind, placebo (sham rTMS) controlled, within-subjects study with crossover between the two active rTMS treatment conditions. An imposed order effect, sham rTMS first, eliminated drift of active treatment into the placebo condition. The primary outcome measures were analogue ratings of tinnitus loudness, annoyance, and awareness, assessed repeatedly at baseline and during treatment, and 64 channel, resting state EEGs collected at baseline and the end of each treatment phase. Active rTMS consisted of 1800 pulses at 110% of motor threshold over temporal cortex delivered at 1Hz and 10Hz over four days. The research design also examined the effect of rTMS immediately following stimulation, regression to the mean in tinnitus ratings made over multiple days, and differences between treatment responders and non-responders. RESULTS: There was no immediate effect of rTMS on tinnitus during a single rTMS session. Regression to the mean in tinnitus ratings occurred over three days of baseline and four days of treatment (both sham and active rTMS). After accounting for regression to the mean in the statistical model, 1Hz rTMS led to a significant decrease in tinnitus awareness from baseline and 10Hz rTMS trended in the same direction, whereas sham rTMS showed little change from baseline other than regression to the mean. Changes from baseline in spectral power of the resting state EEG provided partial support for predictions based on TCD model of tinnitus for active 1 and 10Hz rTMS but not sham rTMS. However, only an increase in beta coherence correlated significantly with a decrease in tinnitus awareness. Changes in the EEG were robust in treatment responders but absent among non-responders and during sham rTMS. CONCLUSIONS: A positive response to rTMS for tinnitus is associated with an rTMS-induced change in beta coherence of the EEG. Increased beta coherence may be a biomarker of the rTMS effect; a "top-down" modulation of the EEG that promotes habituation to tinnitus. Participants whose tinnitus did not improve after rTMS did not show any changes in the EEG.

Impact of caloric test asymmetry on response to treatment in vestibular migraine.

OBJECTIVE: This study aimed to examine the association between caloric asymmetry and response to treatment in patients with vestibular migraine. METHOD: Dizziness Handicap Inventory scores were compared between patients with less than and more than 25 per cent asymmetry (using Cohen effect size) in a cohort of definite vestibular migraine patients who underwent caloric testing between August 2016 and March 2019. RESULTS: A total of 31 patients (mean age: 48.7 ± 20.0 years; mean follow up: 9.1 ± 8.1 months) were included. Mean caloric asymmetry was 15.1 ± 15.6 per cent, with 6 (19.4 per cent) patients having asymmetry more than 25 per cent. Overall, patients experienced significant improvement in Dizziness Handicap Inventory total (d = 0.623 (95 per cent confidence interval, 0.007, 1.216)), emotional domain (d = 0.635 (95 per cent confidence interval, 0.019, 1.229)) and functional domain (d = 0.769 (95 per cent confidence interval, 0.143, 1.367)) but not physical domain (d = 0.227 (95 per cent confidence interval, -0.370, 0.815)) scores. Patients with more than 25 per cent asymmetry had no significant improvement in Dizziness Handicap Inventory scores, whereas those with less than 25 per cent asymmetry had significant improvement in Dizziness Handicap Inventory functional domain scores only (d = 0.636 (95 per cent confidence interval, 0.004, 1.244)). CONCLUSION: Vestibular migraine patients with peripheral vestibular weakness on caloric testing may be less likely to improve after treatment compared with those without.

Pharmacotherapy failure and progression to botulinum toxin injection in vestibular migraine.

OBJECTIVE: Given the lack of evidence on patients with medically refractory vestibular migraine, this study aimed to identify factors associated with pharmacotherapy failure and progression to botulinum toxin injection in vestibular migraine. METHODS: A retrospective cohort study was conducted on definite vestibular migraine patients from September 2015 to July 2019 who completed the Dizziness Handicap Inventory at least six weeks apart.. RESULTS: The study comprised 47 patients (mean age = 50.2 ± 15.8 years), with a mean follow-up time of 6.0 ± 6.0 months. The mean pre-treatment Dizziness Handicap Inventory score was 57.5 ± 23.5, with a mean reduction of 17.3 ± 25.2 (p < 0.001) at last follow up. Oscillopsia (r = 0.458, p = 0.007), failure of first medication (r = 0.518, p = 0.001) and pre-treatment Dizziness Handicap Inventory question 15 (an emotional domain question) score (r = 0.364, p = 0.019) were the only variables significantly correlated with progression to botulinum toxin injection. CONCLUSION: Motion hypersensitivity, failure of first medication, and fear of social stigmatisation suggest a decreased treatment response. These symptoms may require more aggressive treatment at an earlier stage.

International consensus (ICON) on treatment of Ménière's disease.

OBJECTIVE: To present the international consensus for recommendations for Ménière's disease (MD) treatment. METHODS: Based on a literature review and report of 4 experts from 4 continents, the recommendations have been presented during the 21st IFOS congress in Paris, in June 2017 and are presented in this work. RESULTS: The recommendation is to change the lifestyle, to use the vestibular rehabilitation in the intercritic period and to propose psychotherapy. As a conservative medical treatment of first line, the authors recommend to use diuretics and Betahistine or local pressure therapy. When medical treatment fails, the recommendation is to use a second line treatment, which consists in the intratympanic injection of steroids. Then as a third line treatment, depending on the hearing function, could be either the endolymphatic sac surgery (when hearing is worth being preserved) or the intratympanic injection of gentamicin (with higher risks of hearing loss). The very last option is the destructive surgical treatment labyrinthectomy, associated or not to cochlear implantation or vestibular nerve section (when hearing is worth being preserved), which is the most frequent option.

Neural activity during attentional conflict predicts reduction in tinnitus perception following rTMS.

BACKGROUND: Subjective idiopathic tinnitus is an intrusive, distracting, and potentially disabling disorder characterized by phantom perception of sounds. Although tinnitus has no approved pharmacologic treatment, recent evidence supports the use of repetitive transcranial magnetic stimulation (rTMS) to alleviate tinnitus symptoms. OBJECTIVE/HYPOTHESIS: Repetitive TMS delivered over the middle superior temporal gyrus (STG) may alter ratings of tinnitus awareness and annoyance more than loudness due to change in attentional processing. STG has reciprocal connections to regions of the prefrontal cortex that mediate attention. To probe the hypothesized influence of STG stimulation on attention, a subset of patients with tinnitus enrolled in an rTMS clinical trial [n = 12, 9 male, mean (sd) age = 49 (15) years] underwent an attentional conflict task before and after rTMS treatment in a repeated-measures functional magnetic resonance imaging (fMRI) study. METHODS: The Multi-Source Interference Task (MSIT), a Stroop-based visual attentional conflict fMRI task, was used to map participants' neural processing of attentional conflict prior to rTMS intervention (Baseline) and after three rTMS intervention arms: Sham, 1 Hz, and 10 Hz (four sessions per arm, 1800 pulses per session, delivered @110% of the motor threshold over the posterior superior temporal gyrus). RESULTS: All measures of tinnitus severity (awareness, loudness, and annoyance) improved with 1 Hz rTMS intervention; however, the greatest and most robust changes were observed for ratings of tinnitus awareness (mean 16% reduction in severity from Baseline, p < 0.01). The MSIT elicited a similar pattern of neural activation among tinnitus participants at Baseline compared to an independent sample of 43 healthy comparison adults (r = 0.801, p = 0.001). Linear regression with bootstrap resampling showed that greater recruitment of bilateral prefrontal and bilateral parietal regions by MSIT at Baseline corresponded with poorer treatment response. Individual regions' activities explained 37-67% variance in participant treatment response, with left dorsolateral prefrontal cortex's MSIT activity at Baseline explaining the greatest reduction in tinnitus awareness following 1 Hz stimulation. Although left dorsolateral prefrontal cortex activity at Baseline also predicted reduction in tinnitus loudness and annoyance (∼50% variance explained), these symptoms were more strongly predicted by right middle occipital cortex (∼70% variance explained) - suggesting that the neural predictors of symptom-specific treatment outcomes may be dissociable. CONCLUSION: These candidate neural reactivity markers of treatment response have potential clinical value in identifying tinnitus sufferers who would or would not therapeutically benefit from rTMS intervention.

Drug delivery into the cochlear apex: Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral.

BACKGROUND: Administering pharmaceuticals to the scala tympani of the inner ear is a common approach to study cochlear physiology and mechanics. We present here a novel method for in vivo drug delivery in a controlled manner to sealed ears. NEW METHOD: Injections of ototoxic solutions were applied from a pipette sealed into a fenestra in the cochlear apex, progressively driving solutions along the length of scala tympani toward the cochlear aqueduct at the base. Drugs can be delivered rapidly or slowly. In this report we focus on slow delivery in which the injection rate is automatically adjusted to account for varying cross sectional area of the scala tympani, therefore driving a solution front at uniform rate. RESULTS: Objective measurements originating from finely spaced, low- to high-characteristic cochlear frequency places were sequentially affected. Comparison with existing methods(s): Controlled administration of pharmaceuticals into the cochlear apex overcomes a number of serious limitations of previously established methods such as cochlear perfusions with an injection pipette in the cochlear base: The drug concentration achieved is more precisely controlled, drug concentrations remain in scala tympani and are not rapidly washed out by cerebrospinal fluid flow, and the entire length of the cochlear spiral can be treated quickly or slowly with time. CONCLUSIONS: Controlled administration of solutions into the cochlear apex can be a powerful approach to sequentially effect objective measurements originating from finely spaced cochlear regions and allows, for the first time, the spatial origin of CAPs to be objectively defined.

Laterality, frequency and replication of rTMS treatment for chronic tinnitus: pilot studies and a review of maintenance treatment.

This manuscript reports on findings of three open-label, pilot studies and it reviews studies using rTMS as a maintenance treatment for any disorder. The first pilot study examined whether a patient's original treatment response to 1 Hz rTMS over temporal cortex could be replicated by stimulating a homologous region of the opposite hemisphere. The second study examined whether a patient's response to 1 Hz rTMS could be replicated by applying 10 Hz rTMS over the same treatment site. The third study applied a 3-day course of maintenance rTMS, either at 1 or 10 Hz, when subjects indicated that the benefit of their last course of treatment was waning. Patients with bilateral subjective tinnitus of at least 6 months duration were recruited from a prior, sham controlled study with treatment crossover that applied 1 Hz rTMS over temporal cortex. Both treatment responders and non-responders were recruited. Results indicated, first, that the original treatment response, both positive and negative, is replicated after stimulating a homologous region of the opposite hemisphere; second, patients respond similarly to 1 and 10 Hz stimulation of the same treatment site (an exception was one patient who initially failed 1 Hz stimulation but responded positively to 10 Hz stimulation); and, third, maintenance rTMS had a sustained and additive benefit for tinnitus among treatment responders. Conclusions are that rTMS-induced effects on tinnitus are neither hemisphere specific nor frequency dependent; although, different frequencies of rTMS may have greater potency for a given subject. Maintenance treatment is a well tolerated approach with demonstrated feasibility for managing chronic tinnitus in persons who respond positively to an initial course of treatment.

Sham Transcranial Magnetic Stimulation Using Electrical Stimulation of the Scalp.

BACKGROUND: Most methods of sham, repetitive transcranial magnetic stimulation (rTMS) fail to replicate the look, sound, and feel of active stimulation in the absence of a significant magnetic field. OBJECTIVE/HYPOTHESIS: To develop and validate a new method of sham rTMS appropriate for a double-blind, placebo-controlled study with subject crossover. METHODS: The look and sound of active rTMS was replicated using a matched, air-cooled sham TMS coil. Scalp muscle stimulation associated with rTMS was replicated using large rubber electrodes placed over selected muscles. The intensity and pulse width of electrical stimulation necessary to match 1-Hz rTMS was developed in one sample of normal subjects. The sham technique was validated in back-to-back comparisons with active rTMS in new samples of normal subjects who were either naïve or experienced with rTMS. RESULTS: Subjects naïve to TMS could not tell which type of stimulation was active or sham or which was electrical or magnetic. Naïve subjects incorrectly picked sham stimulation as active, when forced to choose, because electrical stimulation felt more focused than magnetic stimulation. Subjects experienced with TMS could correctly identify sham and active stimulation. Experimenters could detect subtle differences between conditions. CONCLUSIONS: This method of sham rTMS closely mimics the look, sound, and feel of active stimulation at 1Hz without creating a significant magnetic field. It is valid for use with naïve subjects and in crossover studies. It can accommodate differences in scalp muscle recruitment at different sites of stimulation, and it could potentially be used with higher frequency stimulation.

Demineralized bone matrix as an alternative for mastoid obliteration and posterior canal wall reconstruction: results in an animal model.

HYPOTHESIS: This study was conducted to evaluate the use of Grafton human demineralized bone matrix as a graft material for mastoid cavity obliteration and canal wall reconstruction in an animal model. BACKGROUND: Canal wall down procedures in the treatment of cholesteatoma may result in a problematic mastoid cavity. Elimination of the mastoid cavity by obliteration or canal wall reconstruction can prevent or correct this problem. Many techniques and implant materials have been used for this application, yet no single material has proven to be ideal. METHODS: Athymic rats received tympanic bulla obliteration and lateral bulla wall reconstruction utilizing the Grafton Putty and Flex formulations, respectively. Wound healing was monitored twice a week. Auditory brainstem evoked responses were obtained 8 weeks after implantation. Nine weeks after implantation, the animals were killed, and histologic sections were prepared. A histologic bone formation score (range 0-4) was determined for each implant. RESULTS: Wound healing occurred without complication. Auditory brainstem response thresholds (average 23.5) fell within the normal range for all ears tested. The average histologic bone formation score for all implants was 3.7. The average scores for obliteration implants and wall reconstruction implants were 3.5 and 3.9, respectively. All wall reconstruction implants underwent partial or total collapse into the bulla. CONCLUSIONS: The high level of bone formation obtained by the use of Grafton implants in this study makes this material a promising resource for use in mastoid obliteration. The use of the material for canal wall reconstruction will likely require a sturdier preparation to prevent collapse into the mastoid cavity.

Prognostic factors in ossiculoplasty: a statistical staging system.

OBJECTIVE: To determine factors that predict hearing results using a standard prosthesis system. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: All patients undergoing ossiculoplasty with the Dornhoffer HAPEX partial and total ossicular replacement prostheses (PORP and TORP) from February 1995 to May 1999 who had documented postoperative follow-up and no congenital atresia or stapes fixation. A total of 185 patients (200 ears), 105 men and 80 women, were evaluated. INTERVENTIONS: Ossiculoplasty with the Dornhoffer prostheses. MAIN OUTCOME MEASURES: Hearing results using a four-frequency pure-tone average air-bone gap (PTA-ABG). Multivariate statistical analysis determined the effect of mucosal status, ossicular chain status, and type of reconstruction techniques on hearing. RESULTS: The PTA-ABGs were 13.4+/-8.1 dB and 14.0+/-8.4 dB for the PORPs (n = 114) and TORPs (n = 86), respectively, which was not statistically different. When the malleus handle was present (n = 126), the PTA-ABG was 11.6+/-6.2 dB, compared with 16.9+/-10.1 dB when it was absent (n = 74), which was statistically significant (p < 0.05). Mucosal fibrosis, drainage, revision ear surgery, and type of surgical procedure had a significant detrimental impact on hearing. The type of pathologic process (perforation vs. cholesteatoma) had no significant impact on hearing results. CONCLUSIONS: The revised staging system, the Ossiculoplasty Outcome Parameter Staging Index, more adequately predicts hearing outcome in this series of 200 cases.

Retrograde mastoidectomy with canal wall reconstruction: a single-stage technique for cholesteatoma removal.

The goal of this retrospective study was to report the preliminary results of the retrograde mastoidectomy technique with canal wall reconstruction used as a primary treatment method for cholesteatoma. This synthesis of canal wall up (CWU) and canal wall down (CWD) techniques was performed in 70 patients (75 ears; 35 pediatric, 40 adult) with an average 45-month follow-up. Surgical intervention involved removal of a portion of the canal wall for exposure and extirpation of the cholesteatoma, followed by reestablishment of the canal wall during reconstruction in a single stage. This leaves the mucosa relatively undisturbed and limits the extent of canal wall removal, facilitating mastoid aeration and preservation of anatomy. Recurrent disease occurred in 5% of cases. The hearing improvement was statistically significant (p < .05), with an average preoperative 4-frequency pure tone average air-bone gap of 27.2 dB improving to 11.5 dB. No patient had a worsening of hearing. The surgery takes less time than traditional techniques, is reproducible and easily taught, and can be universally applied to all cholesteatoma patients as primary treatment.

Unplanned admissions following outpatient otologic surgery: the University of Arkansas experience.

We analyzed the outpatient otologic surgery experience at our institution to identify those factors that are associated with a high risk of postoperative complications that require an unplanned hospital admission. We found that among a group of 662 patients who underwent group II otologic procedures (i.e., tympanoplasty with or without mastoidectomy, stapedotomy, and middle ear exploration), the overall admission rate was 4.7%, of which 3.9% were unplanned. A significantly larger percentage of children were admitted than adults (5.7 vs. 2.3%), primarily for nausea and vomiting. Three factors were significantly associated with unplanned admissions: the type of surgery (tympanomastoidectomy with ossicular reconstruction), the duration of general anesthesia (> 2 hr), and asthma as a coexisting condition. The choice of antiemetic administered (ondansetron or droperidol) and the specific agents used for general anesthesia did not appear to have any significant impact on unplanned admissions. We recommend that the three predisposing factors be taken into consideration when formulating the treatment plan. Scheduling an inpatient procedure for patients who have risk factors for complications requiring hospitalization would avoid the extra costs and stress associated with unplanned admissions.

A case of barotrauma-induced pneumolabyrinth secondary to perilymphatic fistula.

We report the case of a 62-year-old woman who experienced pneumolabyrinth associated with a perilymphatic fistula. Her condition was diagnosed with the help of computed tomography, which detected the presence of an air bubble in the labyrinth, and middle ear exploration, which revealed that clear fluid was emanating from the round window niche in a manner consistent with the presence of a perilymphatic fistula. The niche was repaired with tragal perichondrium and bolstered with Gelfoam.

Surgical management of the atelectatic ear.

OBJECTIVE: The surgical management of the atelectatic ear is controversial because the natural course toward cholesteatoma development cannot be predicted, and hearing acuity remains normal until later in the disease course. Consequently, surgery is often delayed until there is a clear indication, such as hearing loss or frank cholesteatoma development, but such delay often necessitates more extensive surgery. Because earlier intervention appears to be in the best interest of the patient but is often avoided because of near normal hearing levels at this stage, the author proposes a staging system for classification and management of the atelectatic ear. Hearing results and complications in patients undergoing tympanoplasty with or without ossicular reconstruction are reported for patients with type III and IV retractions. STUDY DESIGN: A retrospective study using a computerized otologic database to identify patients who meet the inclusion criteria. SETTING: A tertiary referral center. PATIENTS: A total of 55 patients (63 ears) aged 5 to 78 years underwent cartilage tympanoplasty with or without ossicular reconstruction. INTERVENTIONS: Elevation of the ear drum, followed by cartilage reconstruction of the tympanic membrane, with ossicular reconstruction as indicated. MAIN OUTCOME MEASURES: Postoperative pure tone average air-bone gap for four frequencies (500, 1000, 2000, 4000 Hz) compared with preoperative levels. RESULTS: There was a statistically significant improvement in hearing (p < 0.05). CONCLUSIONS: This staging system offers an effective treatment algorithm for pars tensa retractions and management of type III and IV retractions via cartilage tympanoplasty with or without ossicular reconstruction and is a proven treatment modality.