International consensus (ICON) on treatment of sudden sensorineural hearing loss

© 2018 Elsevier Masson SAS Sudden sensorineural hearing loss (SSNHL) is a common and alarming symptom that often prompts an urgent visit to an ENT specialist. Treatment of SSNHL remains one of the most problematic issues for contemporary otorhinolaryngology: although many meta-analyses and national guidelines have been issued, management is not standardized in terms of medical treatment, and duration and route of administration. We present several methodological suggestions for the study of treatments for SSNHL. These were developed from the existing level of evidence of the main treatments used in SSNHL by experts who convened at the IFOS 2017 ENT World Congress in Paris, France. All panelists agreed that one of the main limitations present in studies on SSNHL is related to the wide heterogeneity, which characterizes both the initial hearing deficit and the amount of hearing recovery. Although evidence of the efficacy of systemic steroids cannot be considered as strong enough to recommend their use, it is still the most widespread primary therapy and can be considered as the current standard of care. Therefore, systemic steroids stand as an adequate control for any innovative treatment. To reduce the number of subjects we suggest that the inclusion criteria should be restricted to moderate to profound levels of hearing loss. The efficacy of trans-tympanic steroids as a salvage therapy was suggested in several reports on small populations and needs to be confirmed with larger randomized controlled trials

Drug diffusion along an intact mammalian cochlea

Intratympanic drug administration depends on the ability of drugs to pass through the round window membrane (RW) at the base of the cochlea and diffuse from this location to the apex. While the RW permeability for many different drugs can be promoted, passive diffusion along the narrowing spiral of the cochlea is limited. Earlier measurements of the distribution of marker ions, corticosteroids and antibiotics demonstrated that the concentration of substances applied to the RW was two to three orders of magnitude higher in the base compared to the apex. The measurements, however, involved perforating the cochlear bony wall and, in some cases, sampling perilymph. These manipulations can change the flow rate of perilymph and lead to intake of perilymph through the cochlear aqueduct, thereby disguising concentration gradients of the delivered substances. In this study, the suppressive effect of salicylate on cochlear amplification via block of the outer hair cell (OHC) somatic motility was utilized to assess salicylate diffusion along an intact guinea pig cochlea in vivo. Salicylate solution was applied to the RW and threshold elevation of auditory nerve responses was measured at different times and frequencies after application. Resultant concentrations of salicylate along the cochlea were calculated by fitting the experimental data using a mathematical model of the diffusion and clearing of salicylate in a tube of variable diameter combined with a model describing salicylate action on cochlear amplification. Concentrations reach a steady-state at different times for different cochlear locations and it takes longer to reach the steady-state at more apical locations. Even at the steady state, the predicted concentration at the apex negligible. Model predictions for the geometry of the longer human cochlea show even higher differences in the steady-state concentrations of the drugs between cochlear base and apex. Our findings confirm conclusions that achieving therapeutic drug concentrations throughout the entire cochlear duct is hardly possible when the drugs are applied to the RW and are distributed via passive diffusion. Assisted methods of drug delivery are needed to reach a more uniform distribution of drugs along the cochlea

Efficacy and safety of bilateral continuous theta burst stimulation (cTBS) for the treatment of chronic tinnitus: design of a three-armed randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Tinnitus, the perception of sound and noise in absence of an auditory stimulus, has been shown to be associated with maladaptive neuronal reorganization and increased activity of the temporoparietal cortex. Transient modulation of tinnitus by repetitive transcranial magnetic stimulation (rTMS) indicated that these areas are critically involved in the pathophysiology of tinnitus and suggested new treatment strategies. However, the therapeutic efficacy of rTMS in tinnitus is still unclear, individual response is variable, and the optimal stimulation area disputable. Recently, continuous theta burst stimulation (cTBS) has been put forward as an effective rTMS protocol for the reduction of pathologically enhanced cortical excitability.</p> <p>Methods</p> <p>48 patients with chronic subjective tinnitus will be included in this randomized, placebo controlled, three-arm trial. The treatment consists of two trains of cTBS applied bilaterally to the secondary auditory cortex, the temporoparietal associaction cortex, or to the lower occiput (sham condition) every working day for four weeks. Primary outcome measure is the change of tinnitus distress as quantified by the Tinnitus Questionnaire (TQ). Secondary outcome measures are tinnitus loudness and annoyance as well as tinnitus change during and after treatment. Audiologic and speech audiometric measurements will be performed to assess potential side effects. The aim of the present trail is to investigate effectiveness and safety of a four weeks cTBS treatment on chronic tinnitus and to compare two areas of stimulation. The results will contribute to clarify the therapeutic capacity of rTMS in tinnitus.</p> <p>Trial registration</p> <p>The trial was registered with the clinical trials register of <url>http://www.clinicaltrials.gov</url> (NCT00518024).</p