Electrical stimulation of the cochlea for treatment of chronic disabling tinnitus: an open-label trial towards the development of an implantable device.

BACKGROUND: Chronic tinnitus affects millions of people globally and constitutes the most commonly compensated disability among military service members in the United States. Existing treatment options largely surround helping patients cope with their disease as opposed to directly suppressing tinnitus perception. The current study investigated the efficacy of electrical stimulation of the cochlea on chronic disabling tinnitus. METHODS: In this single-arm, open-label clinical trial, 22 adult subjects with severe-range asymmetric or unilateral non-pulsatile tinnitus underwent electrical stimulation of the cochlea through use of an extra-cochlear electrode positioned on the cochlear promontory. Each subject underwent 3 stimulation treatments over 3 weeks at 7-day intervals. Tinnitus severity was determined by Tinnitus Handicap Inventory (THI), Tinnitus Functional Index (TFI), and Tinnitus Visual Analog Scale (VAS). Inclusion criteria required subjects have no worse than moderate sensorineural hearing loss determined by pre-enrollment audiometric testing. The primary outcome was nadir post-treatment THI scores, obtained at seven timepoints following electrical stimulation, with clinically significant improvement defined as a decrease of ≥ 7. RESULTS: All 22 (100%) subjects experienced clinically significant improvement in the THI during the study period with a mean decrease in scores of - 31 (95% CI - 38 to - 25) from a baseline of 48. Twenty (91%) experienced clinically significant improvement detectable on at least two of the three tinnitus survey instruments and 17 (77%) experienced clinically significant improvement detectable on all three survey instruments (i.e., THI, TFI, and VAS). Eight (36%) subjects reported either complete (THI of 0; n = 3) or near-complete (THI 1-4; n = 5) suppression of their tinnitus following a stimulation session. Thirteen (59%) subjects reported a nadir following stimulation at or below the threshold for "no or slight handicap" on the THI (≤ 16). No adverse events were observed. CONCLUSIONS: These findings establish the foundation for the development of an extra-cochlear implantable device that delivers electrical stimulation to the cochlea for the treatment of disabling tinnitus. For patients considering device implantation, trans-tympanic cochlear promontory stimulation can facilitate patient selection. Trial Registration ClinicalTrials.gov Identifier: NCT03759834. URL: https://clinicaltrials.gov/ct2/show/NCT03759834.

Mandibular Defect Reconstitution: A Contaminated Caprine Model of Bone Regeneration.

PURPOSE: Mandibular reconstitution with bioabsorbable scaffolds seems feasible with the application of 3-dimensional printing combined with bioactive proteins. As yet, previous studies have been limited in number of animals and have avoided a contaminated defect. We present a caprine model of mandibular defect bone regeneration with a 3-dimensionally printed bioabsorbable scaffold contaminated with oral secretions and explore the impact of bone morphogenic protein in mandibular bone reconstitution. METHODS: A 3-cm, contaminated mandibular defect was generated in 18 goats and stabilized with 2 mandibular reconstruction plates. An uncoated scaffold was placed in 6 goats, and in the final 6 goats, the scaffold was coated with bone morphogenic protein-2. In 6 goats, the defect was left empty. After 12 weeks, the operative site, scaffold, and adjacent mandible were plasticized, sectioned, and evaluated histologically to assess for bone regeneration. RESULTS: The specimens revealed only focal (average of 5.8% of the scaffold pores) and early bone formation in the scaffold-only group. In the scaffold + bone morphogenic protein-2 group, there was more (average of 51.4% of the pores) bone formation. In the periosteum-only group, the ratio of the bone thickness of the defect to that of the normal bone ranged from 0.16 to 0.78. No major infections occurred. CONCLUSIONS: This caprine model serves as an excellent method to assess reconstructive options for contaminated mandibular deficits. Bone regeneration was documented in a 3-cm contaminated caprine mandibular defect reconstructed with a 3-dimensionally printed synthetic scaffold with or without the addition of bone morphogenic protein-2. Bone morphogenic protein-2 significantly augments bone generation in the synthetic scaffold. Residual mandibular periosteum generated bone. Future studies will focus on optimizing vascularization.

Influence of Selection Bias in Survey Studies Derived From a Patient-Focused Organization: A Comparison of Response Data From a Single Tertiary Care Center and the Acoustic Neuroma Association.

BACKGROUND: The Acoustic Neuroma Association (ANA) is a national, nonprofit organization, focused on the education and support of patients with vestibular schwannoma (VS). The aim of the present study is to characterize the profile of ANA survey respondents and compare them with non-ANA patients evaluated at a single tertiary academic referral center to investigate the potential influence of selection bias. METHODS: A prospectively maintained VS quality-of-life (QOL) database, comprised of patients evaluated at the authors' center and members of the ANA, was queried. Demographic variables, patient-reported symptoms and tumor characteristics, as well as patient-reported outcome scores were captured. Health-related QOL was evaluated using the disease-specific Penn Acoustic Neuroma QOL (PANQOL) questionnaire. Multivariable regression models were fitted for PANQOL domain and total scores as well as satisfaction with treatment adjusting for baseline demographics, symptoms, and PANQOL scores. RESULTS: A total of 1,060 patients (802 [76%] ANA respondents) were analyzed. Overall, ANA patients were slightly younger (mean age: 59 vs 60 yr, p = 0.145), more likely to be women (72 vs 55%, p < 0.001), and had a larger tumor size (overall p < 0.001). Furthermore, a significantly higher proportion of ANA patients were more likely to undergo microsurgery (57 vs 21%) or radiation (21 vs 8%) and less likely to be managed with observation (16 vs 65%, overall p < 0.001). A significantly higher proportion of ANA patients reported hearing loss (95 vs 88%, p < 0.001), tinnitus (80 vs 73%, p = 0.034), dizziness (78 vs 64%, p < 0.001), headache (56 vs 45% p = 0.003), and facial paralysis (37 vs 12%, p < 0.001). On multivariable analysis, ANA respondents exhibited significantly lower PANQOL scores for hearing (OR: 0.47, 95% CI: 0.35-0.64, p < 0.001), balance (OR: 0.51, 95% CI: 0.38-0.70, p < 0.001), pain (OR: 0.63, 95% CI: 0.46-0.86, p = 0.004), facial function (OR: 0.58, 95% CI: 0.42-0.80, p = 0.001), energy (OR: 0.44, 95% CI: 0.32-0.59, p < 0.001), anxiety (OR: 0.54, 95% CI: 0.40-0.74, p < 0.001), general (OR: 0.72, 95% CI: 0.53-0.98, p = 0.03), and total QOL (OR: 0.40, 95% CI: 0.30-0.55, p < 0.001). No statistically significant difference was seen with regard to treatment satisfaction.To determine the true clinical relevance of these differences, the two groups were compared using the minimal clinically important difference (MCID) for each domain. MCID is defined as the smallest difference in score in the domain of interest that patients perceive as important, either beneficial or harmful. The domains for hearing, balance, energy, anxiety, and total QOL reached their respective MCID thresholds, indicating that the ANA cohort has QOL scores that are clinically, perceptually worse for these domains compared to the non-ANA group. CONCLUSION: These data help delineate some of the inherent limitations and biases associated with survey studies incorporating data from national patient support organizations. The population profile of ANA survey respondents likely differs significantly from the greater population of patients with VS that may be encountered at a tertiary referral center.

Glioblastoma of the cerebellopontine angle and internal auditory canal mimicking a peripheral nerve sheath tumor: case report.

Glioblastoma (GBM) of the internal auditory canal (IAC) is exceedingly rare, with only 3 prior cases reported in the literature. The authors present the fourth case of cerebellopontine angle (CPA) and IAC GBM, and the first in which the lesion mimicked a vestibular schwannoma (VS) early in its natural history. A 55-year-old man presented with tinnitus, hearing loss, and imbalance. MRI identified a left IAC/CPA lesion measuring 8 mm, most consistent with a benign VS. Over the subsequent 4 months he developed facial weakness. The tumor grew remarkably to 24 mm and surgery was recommended; the main preoperative diagnosis was malignant peripheral nerve sheath tumor (MPNST). Resection proceeded via a translabyrinthine approach with resection of cranial nerves VII and VIII, followed by facial-hypoglossal nerve anastomosis. Intraoperative frozen section suggested malignant spindle cell neoplasm, but final histopathological and molecular testing confirmed the lesion to be a GBM. The authors report the first case in which absence of any brainstem interface effectively excluded a primary parenchymal tumor, in particular GBM, from the differential diagnosis. Given the dramatic differences in treatment and prognoses between malignant glioma and MPNST, this case emphasizes the importance of surgical intervention on an aggressively growing lesion, which provides both the best probability of local control and the critical tissue diagnosis.