OBJECTIVE: Acute sensorineural hearing loss represents a spectrum of conditions characterized by sudden onset hearing loss. The \"Clinical Practice Guidelines for the Diagnosis and Management of Acute Sensorineural Hearing Loss\" were issued as the first clinical practice guidelines in Japan outlining the standard diagnosis and treatment. The purpose of this article is to strengthen the guidelines by adding the scientific evidence including a systematic review of the latest publications, and to widely introduce the current treatment options based on the scientific evidence.
METHODS: The clinical practice guidelines were completed by 1) retrospective data analysis (using nationwide survey data), 2) systematic literature review, and 3) selected clinical questions (CQs). Additional systematic review of each disease was performed to strengthen the scientific evidence of the diagnosis and treatment in the guidelines.
RESULTS: Based on the nationwide survey results and the systematic literature review summary, the standard diagnosis flowchart and treatment options, including the CQs and recommendations, were determined.
CONCLUSIONS: The guidelines present a summary of the standard approaches for the diagnosis and treatment of acute sensorineural hearing loss. We hope that these guidelines will be used in medical practice and that they will initiate further research.

UNASSIGNED: Both tinnitus and hyperacusis, likely triggered by hearing loss, can be attributed to maladaptive plasticity in auditory perception. However, owing to their co-occurrence, disentangling their neural mechanisms proves difficult. We hypothesized that the neural correlates of tinnitus are associated with neural activities triggered by low-intensity tones, while hyperacusis is linked to responses to moderate- and high-intensity tones.
UNASSIGNED: To test these hypotheses, we conducted behavioral and electrophysiological experiments in rats 2 to 8 days after traumatic tone exposure.
UNASSIGNED: In the behavioral experiments, prepulse and gap inhibition tended to exhibit different frequency characteristics (although not reaching sufficient statistical levels), suggesting that exposure to traumatic tones led to acute symptoms of hyperacusis and tinnitus at different frequency ranges. When examining the auditory cortex at the thalamocortical recipient layer, we observed that tinnitus symptoms correlated with a disorganized tonotopic map, typically characterized by responses to low-intensity tones. Neural correlates of hyperacusis were found in the cortical recruitment function at the multi-unit activity (MUA) level, but not at the local field potential (LFP) level, in response to moderate- and high-intensity tones. This shift from LFP to MUA was associated with a loss of monotonicity, suggesting a crucial role for inhibitory synapses.
UNASSIGNED: Thus, in acute symptoms of traumatic tone exposure, our experiments successfully disentangled the neural correlates of tinnitus and hyperacusis at the thalamocortical recipient layer of the auditory cortex. They also suggested that tinnitus is linked to central noise, whereas hyperacusis is associated with aberrant gain control. Further interactions between animal experiments and clinical studies will offer insights into neural mechanisms, diagnosis and treatments of tinnitus and hyperacusis, specifically in terms of long-term plasticity of chronic symptoms.

Hearing loss is well known to cause plastic changes in the central auditory system and pathological changes such as tinnitus and hyperacusis. Impairment of inner ear functions is the main cause of hearing loss. In aged individuals, not only inner ear dysfunction but also senescence of the central nervous system is the cause of malfunction of the auditory system. In most cases of hearing loss, the activity of the auditory nerve is reduced, but that of the successive auditory centers is increased in a compensatory way. It has been reported that activity changes occur in the inferior colliculus (IC), a critical nexus of the auditory pathway. The IC integrates the inputs from the brainstem and drives the higher auditory centers. Since abnormal activity in the IC is likely to affect auditory perception, it is crucial to elucidate the neuronal mechanism to induce the activity changes of IC neurons with hearing loss. This review outlines recent findings on hearing-loss-induced plastic changes in the IC and brainstem auditory neuronal circuits and discusses what neuronal mechanisms underlie hearing-loss-induced changes in the activity of IC neurons. Considering the different causes of hearing loss, we discuss age-related hearing loss separately from other forms of hearing loss (non-age-related hearing loss). In general, the main plastic change of IC neurons caused by both age-related and non-age-related hearing loss is increased central gain. However, plastic changes in the IC caused by age-related hearing loss seem to be more complex than those caused by non-age-related hearing loss.

Chronic tinnitus is a debilitating condition with very few management options. Acoustic trauma that causes tinnitus has been shown to induce neuronal hyperactivity in multiple brain areas in the auditory pathway, including the inferior colliculus. This neuronal hyperactivity could be attributed to an imbalance between excitatory and inhibitory neurotransmission. However, it is not clear how the levels of neurotransmitters, especially neurotransmitters in the extracellular space, change over time following acoustic trauma and the development of tinnitus. In the present study, a range of amino acids were measured in the inferior colliculus of rats during acoustic trauma as well as at 1 week and 5 months post-trauma using in vivo microdialysis and high-performance liquid chromatography. Amino acid levels in response to sound stimulation were also measured at 1 week and 5 months post-trauma. It was found that unilateral exposure to a 16 kHz pure tone at 115 dB SPL for 1 h caused immediate hearing loss in all the animals and chronic tinnitus in 58 % of the animals. Comparing to the sham condition, extracellular levels of GABA were significantly increased at both the acute and 1 week time points after acoustic trauma. However, there was no significant difference in any of the amino acid levels measured between sham, tinnitus positive and tinnitus negative animals at 5 months post-trauma. There was also no clear pattern in the relationship between neurochemical changes and sound frequency/acoustic trauma/tinnitus status, which might be due to the relatively poorer temporal resolution of the microdialysis compared to electrophysiological responses.

Efferent brain-stem neurons release acetylcholine to desensitize cochlear hair cells and can protect the inner ear from acoustic trauma. That protection is absent from knockout mice lacking efferent inhibition and is stronger in mice with a gain-of-function point mutation of the hair cell-specific nicotinic acetylcholine receptor. The present work uses viral transduction of gain-of-function receptors to restore acoustic prophylaxis to the knockout mice. Widespread postsynaptic expression of the transgene was visualized in excised tissue with a fluorophore-conjugated peptide toxin that binds selectively to hair cell acetylcholine receptors. Viral transduction into efferent knockout mice reduced the temporary hearing loss measured 1 day post acoustic trauma. The acoustic evoked-response waveform (auditory brain-stem response) recovered more rapidly in treated mice than in control mice. Thus, both cochlear amplification by outer hair cells (threshold shift) and afferent signaling (evoked-response amplitude) in knockout mice were protected by viral transduction of hair cell acetylcholine receptors. Gene therapy to strengthen efferent cochlear feedback could be complementary to existing and future therapies to prevent hearing loss, including ear coverings, hearing aids, single-gene repair, or small-molecule therapies.

Noise induced hearing loss affects around 5% of the population and acoustic trauma to military personnel accounts for 30% of all injuries inflicted during active service. Initial treatment for acoustic trauma involves administration of steroids, however there are no studies regarding oral steroid regimens for best outcomes. Comparing and elucidating the benefits of four oral steroid regimens on hearing gain in patients with acute acoustic trauma. A prospective study of 4 different steroid regimens was done in 200 soldiers from July 2014 - July 2020. In the first group, oral Prednisolone 60 mg was administered for 6 days, in the second group for 8 days, in the third group for 10 days and in the fourth group for 12 days. Medication was tapered over the next 5 days in all the groups. Data analysed included demographics, Pure Tone Audiograms at admission and at 4 weeks, time of reporting to hospital, onset of treatment and type of treatment given. Multivariate linear regression model was done to consider the risk factors responsible for average hearing gain at all pure tones. Box-and-whisker plot, Mann-Whitney-Wilcoxon test, Kruskal Wallis test, Reciever Operating Characteristic curve were used to analyse the independent samples. p value of < 0.05 was considered statistically significant. Age, time of onset of prednisolone therapy and acoustic trauma due to blast or gunshot injury did not show correlation (R2 = 0.01, 0.01 and 0.35 respectively and p = 0.09, 0.71, 0.80 respectively). Prednisolone therapy, average initial hearing at pure tones were considered as factors responsible for hearing gain as they showed correlation (R2 = 0.22, and 0.34 respectively and p < 0.001 and < 0.01 respectively). Significant hearing gain was found in all groups. The hearing gain was statistically better in group 3 and 4 as compared to group 1 and 2. There was no statistically significant difference in hearing gain between groups 3 and 4. So there was no additional advantage of giving 60 mg oral prednisolone for more than 10 days. The best oral prednisolone regimen recommended is 60 mg/day for 10 days which is tapered over the next 5 days.

Studies have shown that phosphatase and tensin homolog deleted on chromosome ten (PTEN) participates in the regulation of cochlear hair cell survival. Bisperoxovanadium protects against neurodegeneration by inhibiting PTEN expression. However, whether bisperoxovanadium can protect against noise-induced hearing loss and the underlying mechanism remains unclear. In this study, we established a mouse model of noise-induced hearing loss by exposure to 105 dB sound for 2 hours. We found that PTEN expression was increased in the organ of Corti, including outer hair cells, inner hair cells, and lateral wall tissues. Intraperitoneal administration of bisperoxovanadium decreased the auditory threshold and the loss of cochlear hair cells and inner hair cell ribbons. In addition, noise exposure decreased p-PI3K and p-Akt levels. Bisperoxovanadium preconditioning or PTEN knockdown upregulated the activity of PI3K-Akt. Bisperoxovanadium also prevented H2O2-induced hair cell death by reducing mitochondrial reactive oxygen species generation in cochlear explants. These findings suggest that bisperoxovanadium reduces noise-induced hearing injury and reduces cochlear hair cell loss.

We investigated the effectiveness of N-acetyl cysteine (NAC) and curcumin, which have known antioxidant and anti-inflammatory effects, in reducing acoustic trauma. We randomly divided 40 adult male rats into four groups: a control group (group 1), a curcumin group (group 2), a NAC group (group 3), and an ethyl alcohol group (group 4). The rats were exposed to 110 dB sound at a frequency of 4 kHz for 2 h to simulate acoustic trauma. Group 1, group 2, group 3, and group 4 received 1 ml saline, 200 mg/kg curcumin, 350 mg/kg NAC, or 1 ml ethyl alcohol, respectively, intraperitoneally 30 min before and 24 and 48 h after acoustic trauma. Distortion product otoacoustic emissions (DPOAEs) were recorded before and after the acoustic trauma, and 72 h after drug administration. In group 2, signal-to-noise ratio (SNR) values in frequencies of 1000 Hz, 1500 Hz, and 4000 Hz decreased in the second measurements when compared to the first, and showed improvements in the third measurements in comparison to the second ones. In group 3, SNR values decreased in the second measurements, but only the values at 6000 Hz were found to be statistically significant (p = 0.007). The values in the third measurements were statistically significant when compared to the second ones. There was a statistically significant difference in the third measurements in both groups 2 and 3, possibly due to curcumin and NAC treatment. This study showed that curcumin and NAC may be effective against noise-induced hearing loss.

The pathophysiological mechanisms of noise-induced hearing loss remain unknown. Identifying biomarkers of noise-induced hearing loss may increase the understanding of pathophysiological mechanisms of deafness, allow for a more precise diagnosis, and inform personalized treatment. Emerging techniques such as metabolomics can help to identify these biomarkers. The objective of the present study was to investigate immediate-early changes in the perilymph metabolome following acoustic trauma. Metabolomic analysis was performed using liquid chromatography coupled to mass spectrophotometry to analyze metabolic changes in perilymph associated with noise-induced hearing loss. Sheep (n = 6) were exposed to a noise designed to induce substantial hearing loss. Perilymph was collected before and after acoustic trauma. Data were analyzed using univariate analysis and a supervised multivariate analysis based on partial least squares discriminant analysis. A metabolomic analysis showed an abundance of 213 metabolites. Four metabolites were significantly changed following acoustic trauma (Urocanate (p = 0.004, FC = 0.48), S-(5\'-Adenosyl)-L-Homocysteine (p = 0.06, FC = 2.32), Trigonelline (p = 0.06, FC = 0.46) and N-Acetyl-L-Leucine (p = 0.09, FC = 2.02)). The approach allowed for the identification of new metabolites and metabolic pathways involved with acoustic trauma that were associated with auditory impairment (nerve damage, mechanical destruction, and oxidative stress). The results suggest that metabolomics provides a powerful approach to characterize inner ear metabolites which may lead to identification of new therapies and therapeutic targets.

The auditory phantom sensation of tinnitus is associated with neural hyperactivity. Modulating this hyperactivity using repetitive transcranial magnetic stimulation (rTMS) has shown beneficial effects in human studies. Previously, we investigated rTMS in a tinnitus animal model and showed that rTMS over prefrontal cortex (PFC) attenuated tinnitus soon after treatment, likely via indirect effects on auditory pathways. Here, we explored the duration of these beneficial effects. Acoustic trauma was used to induce hearing loss and tinnitus in guinea pigs. Once tinnitus developed, high-frequency (20 Hz), high-intensity rTMS was applied over PFC for two weeks (weekdays only; 10 min/day). Behavioral signs of tinnitus were monitored for 6 weeks after treatment ended. Tinnitus developed in 77% of animals between 13 and 60 days post-trauma. rTMS treatment significantly reduced the signs of tinnitus at 1 week on a group level, but individual responses varied greatly at week 2 until week 6. Three (33%) of the animals showed the attenuation of tinnitus for the full 6 weeks, 45% for 1-4 weeks and 22% were non-responders. This study provides further support for the efficacy of high-frequency repetitive stimulation over the PFC as a therapeutic tool for tinnitus, but also highlights individual variation observed in human studies.