A mouse model of autoimmune inner ear disease without endolymphatic hydrops.

Autoimmune inner ear disease (AIED) is an organ-specific disease characterized by irreversible, prolonged, and progressive hearing and equilibrium dysfunctions. The primary symptoms of AIED include asymmetric sensorineural hearing loss accompanied by vertigo, aural fullness, and tinnitus. AIED is divided into primary and secondary types. Research has been conducted using animal models of rheumatoid arthritis (RA), a cause of secondary AIED. However, current models are insufficient to accurately analyze vestibular function, and the mechanism underlying the onset of AIED has not yet been fully elucidated. Elucidation of the mechanism of AIED onset is urgently needed to develop effective treatments. In the present study, we analyzed the pathogenesis of vertigo in autoimmune diseases using a mouse model of type II collagen-induced RA. Auditory brain stem response analysis demonstrated that the RA mouse models exhibited hearing loss, which is the primary symptom of AIED. In addition, our vestibulo-oculomotor reflex analysis, which is an excellent vestibular function test, accurately captured vertigo symptoms in the RA mouse models. Moreover, our results revealed that the cause of hearing loss and vestibular dysfunction was not endolymphatic hydrops, but rather structural destruction of the organ of Corti and the lateral semicircular canal ampulla due to an autoimmune reaction against type II collagen. Overall, we were able to establish a mouse model of AIED without endolymphatic hydrops. Our findings will help elucidate the mechanisms of hearing loss and vertigo associated with AIED and facilitate the development of new therapeutic methods.

Comparison of the efficacy of the Epley maneuver and repeated Dix-Hallpike tests for eliminating positional nystagmus: A multicenter randomized study.

Background and objectives: Patients with benign paroxysmal positional vertigo of the posterior canal (pc-BPPV) exhibit BPPV fatigue, where the positional nystagmus diminishes with the repeated performance of the Dix-Hallpike test (DHt). BPPV fatigue is thought to be caused by the disintegration of lumps of otoconial debris into smaller parts and can eliminate positional nystagmus within a few minutes [similar to the immediate effect of the Epley maneuver (EM)]. In this study, we aimed to show the non-inferiority of the repeated DHt to the EM for eliminating positional nystagmus after 1 week. Methods: This multicenter, randomized controlled clinical trial was designed based on the CONSORT 2010 guidelines. Patients who had pc-BPPV were recruited and randomly allocated to Group A or Group B. Patients in Group A were treated using the EM, and patients in Group B were treated using repeated DHt. For both groups, head movements were repeated until the positional nystagmus had been eliminated (a maximum of three repetitions). After 1 week, the patients were examined to determine whether the positional nystagmus was still present. The groups were compared in terms of the percentage of patients whose positional nystagmus had been eliminated, with the non-inferiority margin set at 15%. Results: Data for a total of 180 patients were analyzed (90 patients per group). Positional nystagmus had been eliminated in 50.0% of the patients in Group A compared with 47.8% in Group B. The upper limit of the 95% confidence interval for the difference was 14.5%, which was lower than the non-inferiority margin. Discussion: This study showed the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week in patients with pc-BPPV and that even the disintegration of otoconial debris alone has a therapeutic effect for pc-BPPV. Disintegrated otoconial debris disappears from the posterior canal because it can be dissolved in the endolymph or returned to the vestibule via activities of daily living. Classification of evidence: This study provides Class II evidence of the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week. Registration number: UMIN000016421.

Stratification of patients with Menière's disease based on eye movement videos recorded from the beginning of vertigo attacks and contrast-enhanced MRI findings.

Purpose: Diagnosis of Menière's disease (MD) relies on subjective factors and the patients diagnosed with MD may have heterogeneous pathophysiologies. This study aims to stratify MD patients using two objective data, nystagmus videos and contrast-enhanced magnetic resonance imaging (CE-MRI). Methods: This is a retrospective cross-sectional study. According to the Japan Society for Equilibrium Research criteria (c-JSER), adults diagnosed with definite MD and who obtained videos recorded by portable nystagmus recorder immediately following vertigo attacks and underwent CE-MRI of the inner ear were included (ss = 91). Patients who obtained no nystagmus videos, who had undergone sac surgery, and those with long examination intervals were excluded (n = 40). Results: The gender of the subjects was 22 males and 29 females. The age range was 20-82 y, with a median of 54 y. Endolymphatic hydrops (EH) were observed on CE-MRI in 84% (43 patients). Thirty-one patients had unilateral EH. All of them demonstrated EH on the side of the presence of cochlear symptoms. The number of patients who had both nystagmus and EH was 38. Five patients only showed EH and 5 patients only exhibited nystagmus, while 3 patients did not have either. Of the 43 nystagmus records, 32 showed irritative nystagmus immediately after the vertigo episode. The direction of nystagmus later reversed in 44% of cases over 24 h. Conclusion: Patients were stratified into subgroups based on the presence or absence of EH and nystagmus. The side with cochlear symptoms was consistent with EH. The c-JSER allows for the diagnosis of early-stage MD patients, and it can be used to treat early MD and preserve hearing; however, this approach may also include patients with different pathologies.

Therapeutic strategy for facial paralysis based on the combined application of Si-based agent and methylcobalamin.

Facial paralysis results in the decline in the generation of facial expressions and is attributed to several causes. Intractable facial paralysis has a poor prognosis, and new treatments are required. Facial paralysis results in the decline in the generation of facial expressions and is attributed to several causes. Reactive oxygen species can inhibit peripheral nerve regeneration after injury. Therefore, the administration of an appropriate antioxidant can promote nerve regeneration. Silicon (Si)-based agents can react with water to generate antioxidant hydrogen. Oral administration of Si-based agents can effectively alleviate symptoms of disease models associated with oxidative stress. Thus, we orally administered a Si-based agent to a facial paralysis model mice to investigate whether promotion of nerve regeneration occurred. The combined administration of methylcobalamin (MeCbl) with the Si-based agent was also investigated. The Si-based agent improved the clinical score evaluation of facial paralysis. Electroneuronography and immunostaining showed that the Si-based agent promoted myelination and recovery of facial nerve function. Furthermore, in the drug-administered group, oxidative stress associated with facial nerve injury was reduced more than that in the non-administered group. The clinical score evaluation, neuroregeneration effect, and reduction of oxidative stress were improved in the combination group compared to the single administration group. The Si-based agent could rapidly improve the disappearance of facial expressions by promoting myelin sheath formation and alleviating oxidative stress. Combination therapy with a Si-based agent and MeCbl should improve the prognosis and treatment of intractable facial paralysis.

Benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is characterized by positional vertigo (brief attacks of rotatory vertigo triggered by head position changes in the direction of gravity) and is the most common peripheral cause of vertigo. There are two types of BPPV pathophysiology: canalolithiasis and cupulolithiasis. In canalolithiasis, otoconial debris is detached from the otolithic membrane and floats freely within the endolymph of the canal. In cupulolithiasis, the otoconial debris released from the otolithic membrane settles on the cupula of the semicircular canal and the specific gravity of the cupula is increased. Consensus has been reached regarding three subtypes of BPPV: posterior-canal-type BPPV (canalolithiasis), lateral-canal-type BPPV (canalolithiasis) and lateral-canal-type BPPV (cupulolithiasis). In the interview-based medical examination of BPPV, questions regarding the characteristics of vertigo, triggered movement of vertigo, duration of vertigo and cochlear symptoms during vertigo attacks are important for the diagnosis of BPPV. The Dix-Hallpike test is a positioning nystagmus test used for diagnosis of posterior-canal-type BPPV. The head roll test is a positional nystagmus test used for diagnosis of lateral-canal-type BPPV. When the Dix-Hallpike test is repeated, positional nystagmus and the feeling of vertigo typically become weaker. This phenomenon is called BPPV fatigue. The effect of BPPV fatigue typically disappears within 30 min, at which point the Dix-Hallpike test again induces clear positional nystagmus even though BPPV fatigue had previously caused the positional nystagmus to disappear. For the treatment of BPPV, sequential head movements of patients can cause the otoconial debris in the semicircular canal to move to the utricle. This series of head movements is called the canalith repositioning procedure (CRP). The appropriate type of CRP depends on the semicircular canal in which the otoconial debris is located. The CRP for posterior-canal-type BPPV is called the Epley maneuver, and the CRP for lateral-canal-type BPPV is called the Gufoni maneuver. Including a time interval between each head position in the Epley maneuver reduces the immediate effect of the maneuver. This finding can inform the development of methods for reducing the effort exerted by doctors and the discomfort experienced by patients with posterior-canal-type BPPV during the Epley maneuver.

Antivertiginous Effect of Caloric Stimulation for Acute Peripheral Vertigo.

OBJECTIVE: To clarify therapeutic effect of caloric stimulation for acute peripheral vertigo. PATIENTS: Two patients with acute peripheral vertigo accompanied by spontaneous nystagmus. INTERVENTIONS: Therapeutic. MAIN OUTCOMES AND MEASURES: Changes in the maximum slow phase velocity of spontaneous nystagmus and subjective vertigo. RESULTS: Reduction in the maximum slow phase velocity of spontaneous nystagmus and mitigation of subjective vertigo was observed in both patients. CONCLUSION: Caloric stimulation could be one potential option as a suppressant for acute peripheral vertigo.

The effect of cochlear implants on cognitive function in older adults: A prospective, longitudinal 2-year follow-up study.

OBJECTIVES: It is shown that eliminating hearing loss in mid-life may reduce the risk for deterioration in cognitive function. Cochlear implantation (CI) is the only available therapy that can eliminate hearing loss in patients who suffer from profound sensorineural hearing loss. This suggests there may be positive effects of hearing level on cognition in older adults following CI. Therefore, the purpose of this study is to clarify whether cognitive function can be improved or maintained using cochlear implants in older adult patients with hearing impairments. METHODS: Data for patients that underwent CI surgery for profound bilateral sensorineural hearing loss were collected prospectively. Patients aged 65 years and older were recruited at our university hospital from 2013 to 2017. Twenty-one patients (age range: 65-80 years) were included in this study. The primary outcome measurement was the change in cognitive function three points assessed by Mini-Mental State Examination (MMSE): preoperatively, and at 1 and 2 years after surgery. The secondary outcome measurements were the followings; the Nijmegen Cochlear Implant Questionnaire (NCIQ), the Self-Rating Depression Scale (SDS), and hearing and speech recognition threshold assessment before CI, and 1 and 2 years after CI. Differences in MMSE scores were compared for statistical significance using the Friedman test. The Wilcoxon signed-rank test was used as a post hoc test. Possible correlations between MMSE scores and NCIQ subdomain scores 2 years after surgery were evaluated with Spearman's tests. Statistical significance was defined as a p-value <0.05. RESULTS: CI recipients showed significant improvement in MMSE scores. This improvement peaked 1 year after CI surgery. The postoperative MMSE score was correlated with the NCIQ speech production score but not with the other five NCIQ subdomains. There was no correlation between MMSE score and speech recognition. CONCLUSION: Speech production is important to improve cognitive function after CI, and this improvement peaked 1 year after CI. Although severe or profound hearing loss in older adults worsens the natural course of cognitive function decline, CI has positive impacts on cognitive function even if MMSE scores decrease 1 year after the peak (i.e., 2 years after CI). Talking with others based on hearing is crucial to improve cognitive function. We should encourage older adult patients to take many opportunities to talk with others after CI surgery.

COVID­19 and peritonsillar abscess co­infection: A case report.

Coronavirus disease 2019 (COVID-19) generally presents with fever, shortness of breath and a sore throat. These symptoms are also common in oral and pharyngeal infections, such as peritonsillar abscess (PA). The present study describes a case of PA and COVID-19 co-infection. Although COVID-19 was initially suspected in the patient due to the presenting symptoms of fever, sore throat, dysgeusia and dysosmia, an oral examination and computed tomography scan detected PA. The patient was conservatively managed with intravenous antibiotics without transoral drainage of the abscess. Anti-COVID-19 medication was not administered as the COVID-19 infection in the patient was not severe. Laboratory findings revealed high levels of leukocytes, C-reactive protein (CRP) and procalcitonin. On the whole, the association between laboratory findings (including leukocyte count, CRP and procalcitonin levels) and bacterial co-infection with COVID-19 remains unclear, and further studies are warranted. Oral examinations and transoral procedures are often avoided due to the high risk of the aerosolisation of COVID-19 viral particles. However, an appropriate evaluation is essential in order to avoid the underdiagnosis of life-threatening bacterial infections that co-exist with COVID-19.

Daple deficiency causes hearing loss in adult mice by inducing defects in cochlear stereocilia and apical microtubules.

The V-shaped arrangement of hair bundles on cochlear hair cells is critical for auditory sensing. However, regulation of hair bundle arrangements has not been fully understood. Recently, defects in hair bundle arrangement were reported in postnatal Dishevelled-associating protein (ccdc88c, alias Daple)-deficient mice. In the present study, we found that adult Daple-/- mice exhibited hearing disturbances over a broad frequency range through auditory brainstem response testing. Consistently, distorted patterns of hair bundles were detected in almost all regions, more typically in the basal region of the cochlear duct. In adult Daple-/- mice, apical microtubules were irregularly aggregated, and the number of microtubules attached to plasma membranes was decreased. Similar phenotypes were manifested upon nocodazole treatment in a wild type cochlea culture without affecting the microtubule structure of the kinocilium. These results indicate critical role of Daple in hair bundle arrangement through the orchestration of apical microtubule distribution, and thereby in hearing, especially at high frequencies.

Development of a new method for assessing otolith function in mice using three-dimensional binocular analysis of the otolith-ocular reflex.

In the interaural direction, translational linear acceleration is loaded during lateral translational movement and gravitational acceleration is loaded during lateral tilting movement. These two types of acceleration induce eye movements via two kinds of otolith-ocular reflexes to compensate for movement and maintain clear vision: horizontal eye movement during translational movement, and torsional eye movement (torsion) during tilting movement. Although the two types of acceleration cannot be discriminated, the two otolith-ocular reflexes can distinguish them effectively. In the current study, we tested whether lateral-eyed mice exhibit both of these otolith-ocular reflexes. In addition, we propose a new index for assessing the otolith-ocular reflex in mice. During lateral translational movement, mice did not show appropriate horizontal eye movement, but exhibited unnecessary vertical torsion-like eye movement that compensated for the angle between the body axis and gravito-inertial acceleration (GIA; i.e., the sum of gravity and inertial force due to movement) by interpreting GIA as gravity. Using the new index (amplitude of vertical component of eye movement)/(angle between body axis and GIA), the mouse otolith-ocular reflex can be assessed without determining whether the otolith-ocular reflex is induced during translational movement or during tilting movement.

Effect of Sitting Position vs. Supine Position With the Head Turned to the Affected Side on Benign Paroxysmal Positional Vertigo Fatigue.

Objective: In benign paroxysmal positional vertigo (BPPV), positional nystagmus becomes generally weaker when the Dix-Hallpike test is repeated. This phenomenon is termed BPPV fatigue. We previously reported that the effect of BPPV fatigue deteriorates over time (i.e., the positional nystagmus is observed again after maintaining a sitting head position). The aim of this study was to investigate whether the effect of BPPV fatigue attenuates after maintaining a supine position with the head turned to the affected side. Methods: Twenty patients with posterior-canal-type BPPV were assigned to two groups. Group A received Dix-Hallpike test, were returned to the sitting position (reverse Dix-Hallpike test) with a sitting head position for 10 min, and then received a second Dix-Hallpike test. Group B received Dix-Hallpike test, were kept in the supine position with the head turned to the affected side for 10 min, and then received reverse Dix-Hallpike test followed by the second Dix-Hallpike test. The maximum slow phase eye velocity (MSPEV) of positional nystagmus induced by the first, reverse, and second Dix-Hallpike test were analyzed. Results: The ratio of MSPEV of the positional nystagmus induced by the second Dix-Hallpike test relative to the first Dix-Hallpike test was significantly smaller in group B than that in group A. There was no difference in the MSPEV of the positional nystagmus induced by the reverse Dix-Hallpike test between group A and B. Conclusions: The effect of BPPV fatigue is continued by maintaining a supine position with the head turned to the affected side, while the effect is weakened by maintaining a sitting head position. On the basis of the most widely accepted theory of the pathophysiology of BPPV fatigue, in which the particles become dispersed along the canal during head movement in the Dix-Hallpike test, we found an inconsistency whereby the dispersed otoconial debris return to a mass during the sitting position but do not return to a mass in the supine position with the head turned to the affected side. Future studies are required to determine the exact pathophysiology of BPPV fatigue. Classification of Evidence: 2b.

Phosphorylation of MYL12 by Myosin Light Chain Kinase Regulates Cellular Shape Changes in Cochlear Hair Cells.

The organ of Corti is an auditory organ located in the cochlea, comprising hair cells (HCs) and other supporting cells. Cellular shape changes of HCs are important for the development of auditory epithelia and hearing function. It was previously observed that HCs and inner sulcus cells (ISCs) demonstrate cellular shape changes similar to the apical constriction of the neural epithelia. Apical constriction is induced via actomyosin cable contraction in the apical junctional complex and necessary for the physiological function of the epithelium. Actomyosin cable contraction is mainly regulated by myosin regulatory light chain (MRLC) phosphorylation by myosin light chain kinase (MLCK). However, MRLC and MLCK isoforms expressed in HCs and ISCs are unknown. Hence, we investigated the expression patterns and roles of MRLCs and MLCKs in HCs. Droplet digital PCR revealed that HCs expressed MYL12A/B and MYL9, which are non-muscle MRLC and smooth muscle MLCK (smMLCK), respectively. Immunofluorescence staining throughout the organ of Corti demonstrated that only MYL12 was expressed in the apical portion of HCs, whereas MYL12 and MYL9 were expressed on ISCs. In addition, purified MYL12B was phosphorylated by smMLCK in vitro, and the harvested HCs contained phosphorylated MYL12. Furthermore, accompanied by the expansion of the cell area of outer HCs, MYL12 phosphorylation was reduced by ML-7, which is an inhibitor of smMLCK. In conclusion, MYL12 phosphorylation by smMLCK contributed to the apical constriction-like cellular shape change of HCs possibly relating to the development of auditory epithelia and hearing function.

Platform posturography of patients with peripheral vestibular dysfunction in the non-acute phase of vertigo.

OBJECTIVE: Posturography (PG) shows various patterns corresponding to a patient's equilibrium condition; however, PG is not useful for the differential diagnosis of peripheral vestibular diseases (PVDs). The aim of this study was to identify parameters of PG that can distinguish between PVDs. METHODS: The differences in PG parameters between PVDs were evaluated retrospectively. Two hundred and two patients with Ménière's disease (MD), 154 patients with benign paroxysmal positional vertigo (BPPV), 20 patients with sudden sensorineural hearing loss with vertigo (SSNHLwV), and 31 patients with vestibular neuritis (VN) underwent PG during the non-acute phase of vertigo, from January 2010 to March 2017. RESULTS: The velocity of body oscillation of BPPV patients with eyes open and closed were significantly faster than those of MD patients with eyes open (p < 0.001) and closed (p = 0.033). The velocity of body oscillation of VN patients with eyes open was significantly faster than that of MD patients with eyes open (p = 0.0083). There were no significant differences among the other PG parameters between PVDs. Although there were significant differences among the velocity with eyes open and closed between males and females (eye open: p = 0.0009, eye close: p < 0.0001), there was no significant difference in the ratio of males to females among PVDs (p = 0.1834). Therefore, the ratio did not influence the difference in velocity among PVDs. Patient age correlated with the velocity with eyes open (p < 0.001) and with eyes closed (p < 0.001). Post-hoc analysis revealed significant differences in patient age, and comparisons of MD and BPPV, MD and SSNHLwV, BPPV and VN, and VN and SSNHLwV. Therefore, we performed multiple regression analysis to determine whether the significant differences in the velocity of body oscillation among PVDs were caused by the difference in age distribution between PVD groups, rather than by differences in the PVDs themselves. There were correlations between age and the velocity of body oscillation with eyes open (p < 0.001) and with eyes closed (p < 0.001). There also were correlations between MD or VN and the velocity of body oscillation with eyes open (p = 0.0194). CONCLUSION: There were significant differences in the velocity of body oscillation with eyes open between MD and VN patients. The difference between MD and VN was significant regardless of the age distribution. To distinguish between MD and VN, the velocity of body oscillation with eyes open is a useful PG index.

Vestibular Compensation after Vestibular Dysfunction Induced by Arsanilic Acid in Mice.

When vestibular function is lost, vestibular compensation works for the reacquisition of body balance. For the study of vestibular dysfunction and vestibular compensation, surgical or chemical labyrinthectomy has been performed in various animal species. In the present study, we performed chemical labyrinthectomy using arsanilic acid in mice and investigated the time course of vestibular compensation through behavioral observations and histological studies. The surgical procedures required only paracentesis and storage of 50 µL of p-arsanilic acid sodium salt solution in the tympanic cavity for 5 min. From behavioral observations, vestibular functions were worst at 2 days and recovered by 7 days after surgery. Spontaneous nystagmus appeared at 1 day after surgery with arsanilic acid and disappeared by 2 days. Histological studies revealed specific damage to the vestibular endorgans. In the ipsilateral spinal vestibular nucleus, the medial vestibular nucleus, and the contralateral prepositus hypoglossal nucleus, a substantial number of c-Fos-immunoreactive cells appeared by 1 day after surgery with arsanilic acid, with a maximum increase in number by 2 days and complete disappearance by 7 days. Taken together, these findings indicate that chemical labyrinthectomy with arsanilic acid and the subsequent observation of vestibular compensation is a useful strategy for elucidation of the molecular mechanisms underlying vestibular pathophysiologies.

Clinical significance of cervical and ocular vestibular evoked myogenic potentials in benign paroxysmal positional vertigo: a meta-analysis.

PURPOSE: As the pathological cause of benign paroxysmal positional vertigo (BPPV), the dislocation or degeneration of otoconia in the utricle and saccule is suggested. Vestibular evoked myogenic potential (VEMP) could reflect otolithic dysfunction due to these etiologies of BPPV. The aim of this study was to validate the clinical significance of cervical (c) and ocular (o) VEMP in BPPV by a meta-analysis of previous articles. METHODS: Articles related to BPPV with data on cVEMP and oVEMP were collected. The following keywords were used to search PubMed and Scopus for English language articles: benign paroxysmal positional vertigo or BPPV and vestibular evoked myogenic potential or VEMP. RESULTS: The p13 latency in cVEMP and n1 latency in oVEMP were slightly but significantly prolonged in BPPV patients compared to control patients. AR in oVEMP of BPPV patients also showed higher value than that of control patients. However, the n23 latency and AR in cVEMP and p1 latency in oVEMP showed no significant difference between BPPV and control patients. Furthermore, latencies in VEMPs also showed no significant difference between an affected and a non-affected ear in BPPV patients. CONCLUSIONS: Our results indicated that otolith dysfunction of BPPVs was detected by latencies in VEMPs, and AR in oVEMP more sensitively reflects the difference between affected and non-affected ears in BPPV patients. The otolith dysfunction of BPPV might be induced by the systemic condition. However, the differences of latencies between BPPV patients and control patients were too small to use VEMPs as a prognostic predictor.

Rat Model of Ménière's Attack: Intratympanic Injection of Potassium Chloride Produces Direction-Changing Spontaneous Nystagmus and Hearing Fluctuations.

The major symptoms of Ménière's disease are episodic vertigo, fluctuating hearing loss, and tinnitus. Direction-changing spontaneous nystagmus is a characteristic vestibular finding in Ménière's disease. In the acute stage, spontaneous nystagmus beating to the affected side (irritative nystagmus) is often observed, while paralytic nystagmus beating to the healthy side is found in the chronic stage. This direction-changing nystagmus can be reproduced in guinea pigs by increasing the potassium ion concentration in the perilymph. The objectives of the present study were to examine the effects of increasing the potassium ion concentration of the rat perilymph on hearing and nystagmus. Under isoflurane anesthesia, 22 rats received intratympanic injection of different concentrations of potassium chloride (KCl) solution or distilled water: groups 1, 2, 3, and 4 received saturated (3.4 M) KCl solution, 2 M KCl, 1 M KCl, and distilled water, respectively. The nystagmus direction and number per 15 s were monitored for 150 min. In the other 8 rats, hearing was monitored 30 min and 20 h after intratympanic injection of 2 M KCl (group 5) or distilled water (group 6) using the auditory brainstem responses. Rats in groups 1 and 2 showed spontaneous irritative nystagmus beating to the affected ear followed by paralytic nystagmus beating to the contralateral side. In group 3, irritative nystagmus occurred but paralytic nystagmus was rarely observed. Rats in group 4 showed no nystagmus. Rats in group 5 showed significant hearing impairment 30 min after KCl injection that recovered 20 h later. Control animals in group 6 showed no significant changes in hearing. The reversible hearing impairment with direction-changing spontaneous nystagmus induced by potassium injection into the tympanic cavity in rats was quite similar to that observed in acute Ménière's attacks. This rat model could be used for basic research investigating the pathophysiological mechanisms underlying Ménière's attacks.

Osteoclasts Modulate Bone Erosion in Cholesteatoma via RANKL Signaling.

Cholesteatoma starts as a retraction of the tympanic membrane and expands into the middle ear, eroding the surrounding bone and causing hearing loss and other serious complications such as brain abscess and meningitis. Currently, the only effective treatment is complete surgical removal, but the recurrence rate is relatively high. In rheumatoid arthritis (RA), osteoclasts are known to be responsible for bone erosion and undergo differentiation and activation by receptor activator of NF-κB ligand (RANKL), which is secreted by synovial fibroblasts, T cells, and B cells. On the other hand, the mechanism of bone erosion in cholesteatoma is still controversial. In this study, we found that a significantly larger number of osteoclasts were observed on the eroded bone adjacent to cholesteatomas than in unaffected areas, and that fibroblasts in the cholesteatoma perimatrix expressed RANKL. We also investigated upstream transcription factors of RANKL using RNA sequencing results obtained via Ingenuity Pathways Analysis, a tool that identifies relevant targets in molecular biology systems. The concentrations of four candidate factors, namely interleukin-1ß, interleukin-6, tumor necrosis factor α, and prostaglandin E2, were increased in cholesteatomas compared with normal skin. Furthermore, interleukin-1ß was expressed in infiltrating inflammatory cells in the cholesteatoma perimatrix. This is the first report demonstrating that a larger-than-normal number of osteoclasts are present in cholesteatoma, and that the disease involves upregulation of factors related to osteoclast activation. Our study elucidates the molecular basis underlying bone erosion in cholesteatoma.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Hematologic Markers of Bell's Palsy: A Meta-analysis.

OBJECTIVE: Bell's palsy (BP) is the most common cause of unilateral peripheral facial paralysis, and inflammation has been proposed as the main pathological cause. The study aim was to investigate the relationship between hematologic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and BP. DATA SOURCES: The following key words were used to search PubMed and Scopus for English language articles: Bell's palsy, facial palsy, facial paresis or facial paralysis, neutrophil, lymphocyte, and platelet. STUDY SELECTION: Articles related to BP with NLR or PLR data. DATA EXTRACTION: The data included patient profiles, House-Brackmann score, treatment modality, NLR, and PLR. DATA SYNTHESIS: Seven articles were selected. A random effect model was used to analyze the aggregated data. Six of these articles that included the NLR and two that included the PLR of BP and control patients were analyzed for the difference between BP and control patients. Three articles that included the NLR of the recovery and nonrecovery groups were analyzed for the relationship between NLR and recovery. CONCLUSIONS: The NLR was significantly higher for the BP patients than for the controls. Furthermore, the NLR was significantly lower for the recovery group than for the nonrecovery group. A high NLR was associated with poor prognosis and related to the severity of facial nerve inflammation. There was no significant difference between the PLRs of the BP patients and controls. The NLR, but not the PLR, was found to be a useful prognostic indicator of BP.

Effects of Interval Time of the Epley Maneuver on Immediate Reduction of Positional Nystagmus: A Randomized, Controlled, Non-blinded Clinical Trial.

Objective: The Epley maneuver (EM) has an immediate effect: rapid reduction of positional nystagmus. Benign paroxysmal positional vertigo (BPPV) causes BPPV fatigue, which constitutes fatigability of positional nystagmus and vertigo with repeated performance of the Dix-Hallpike test; notably, BPPV fatigability becomes ineffective over time. We hypothesized that the immediate effect of the EM is caused by BPPV fatigue. Therefore, we suspected that performance of the EM with intervals between head positions would worsen the immediate reduction of positional nystagmus in patients with BPPV, because BPPV fatigability would become ineffective during performance of this therapy. Methods: Forty patients with newly diagnosed BPPV were randomly assigned to the following two groups; one group performed the EM without intervals between positions (group A), and the other group performed the EM with 3 min intervals between positions (group B). The primary outcome measure was the ratio of maximum slow-phase eye velocity (MSPEV) of positional nystagmus soon after the EM, compared with that measured before the EM. Secondary outcome included whether a 30 min interval after the EM enabled recovery of MSPEV of positional nystagmus to the original value. This study followed the CONSORT 2010 reporting standards. Results: In both groups A and B, the immediate effect of the EM could be observed, because MSPEV during the second Dix-Hallpike test was significantly smaller than MSPEV during the first Dix-Hallpike test (p < 0.0001 in group A, p < 0.0001 in group B). The primary outcome measure was larger in group B than in group A (p = 0.0029). The immediate effect faded 30 min later (secondary outcome). Conclusions: This study showed that the EM had an immediate effect both with and without interval time in each head position of the EM. Because setting interval time in each head position of the EM reduced the immediate effect of the EM, interval time during the EM adds less benefit. This finding can reduce the effort exerted by doctors, as well as the discomfort experienced by patients with pc-BPPV, during EM. However, this immediate effect may be caused by BPPV fatigue, and may fade rapidly. Classification of Evidence: 1b.

Effects of cochlear implants on otolith function as evaluated by vestibulo-ocular reflex and vestibular evoked myogenic potentials.

OBJECTIVE: The aim of this study was to investigate whether the insertion of an implant into the cochlea is accompanied by a deterioration in otolith function. Cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP) and linear vestibulo-ocular reflex (lVOR) during eccentric rotation were assessed before and after cochlear implantation (CI) to evaluate otolith function. METHODS: Twelve patients with bilateral severe sensorineural hearing loss who had undergone CI surgery in our hospital between May 2016 and November 2017 were included in this study. cVEMP and oVEMP were assessed using the asymmetry ratio (AR), calculated with the following formula: [(peak-to-peak amplitude calculated as the sum of the p13 and n23 amplitudes in the non-operated side) - (that in the operated side)]/[(that in the non-operated side) + (that in the operated side)]. The ratio of VOR gain during eccentric rotation against VOR gain during center rotation was used to assess lVOR. For eccentric rotation, patients were rotated while displaced from the axis of rotation. At the same time, linear acceleration stimulated the utricle and induced lVOR. All patients underwent cVEMP and oVEMP tests and center and eccentric rotation tests before and about 30days after CI surgery. RESULTS: Three patients with absent cVEMP responses before surgery were excluded, leaving pre-surgery cVEMP results for 9/12 patients. In five of these patients, the AR of cVEMP increased after CI, indicating that saccular function, as evaluated by cVEMP, did not deteriorate significantly postoperatively. One patient with an absent oVEMP response before CI was excluded, leaving pre-surgery oVEMP results for 11/12 patients. In 10 of these patients, the AR of oVEMP increased after CI surgery, indicating that utricular function, as evaluated by oVEMP, deteriorated significantly postoperatively. However, because the ratio of VOR gain during eccentric rotation against VOR gain during center rotation did not become worse after CI, utricular function, as evaluated by lVOR, did not deteriorate significantly postoperatively. Symptoms of vertigo became worse after CI in two of the 12 patients. CONCLUSION: CI does not cause a deterioration in saccular function, as evaluated by cVEMP. Although CI does cause a deterioration in utricular function in oVEMP tests, this is not consistent in lVOR tests. These results indicate that CI causes a slight deterioration in utricular function that is insufficient to cause vertigo or deterioration of lVOR.