Pediatric Ménière's disease with disassociated cochlear and vestibular symptoms: a case report.

Background: Typical Ménière's disease (MD) rarely occurs in childhood. Compared to adults, age-associated changes in vestibular function can occur during infancy and childhood. Previous case reports may have lacked some audiovestibular tests in children. It is worthwhile to follow a child with MD to observe how vertigo and hearing loss could progress under an insufficient vestibular system. Case Description: A 14-year-old pediatric patient with disassociated episodes between vertigo and hearing loss was finally diagnosed with MD. He was diagnosed with probable MD due to lack of objective evidence of hearing loss in his first two admissions. However, in his third admission, he had hearing loss even without attack of vertigo and was finally diagnosed. By listing the patient's audiovestibular auxiliary tests in a chronological order, we might follow the progress of pediatric MD. Gadolinium-enhanced magnetic resonance imaging (Gd-MRI) might be sensitive to reflect endolymphatic hydrops (EH). Medications including corticosteroids might be effective for both hearing loss and vertigo. Conclusions: In pediatric MD, vestibular and cochlear symptoms may occur and progress independently. Audiovestibular evaluation, especially caloric tests and cervical vestibular evoked myogenic potential (cVEMP), can be useful for pediatric MD. Gd-MRI can be sensitive for detecting EH. Both systemic and postauricular administration of corticosteroids might be effective in alleviating vertigo and improving hearing. Prolongation of the follow-up period of pediatric MD is warranted.

Vestibular function and hearing preservation in children following a minimally invasive cochlear implantation.

PURPOSE: This retrospective cohort study aimed to investigate the effect of minimally invasive cochlear implantation (CI) on the vestibular function (VF) and residual hearing (RH) as well as their relationship in pediatric recipients before and after surgery. METHODS: Twenty-four pediatric patients with preoperative low frequency residual hearing (LFRH) (250 or 500 Hz ≤ 80 dB HL) who underwent minimally invasive CI were enrolled. Pure-tone thresholds, the cervical/ocular vestibular-evoked myogenic potential (cVEMP/oVEMP), and video head impulse test (vHIT) were all evaluated in the 24 pediatric patients with preoperative normal VF before and at 1 and 12 months after surgery. The relationship between changes in hearing and VF was analyzed preoperatively and at 1 and 12 months postoperatively. RESULTS: There were no significant differences on VF preservation and hearing preservation (HP) at both 1 and 12 months post-CI (p > 0.05). At 1 month post-CI, the correlations of the variations in vestibulo-ocular reflex (VOR) gains of horizontal semicircular canal (HSC) and posterior semicircular canal (PSC) and the shift in 250 Hz threshold were negatively correlated (r = - 0.41, p = 0.04 and r = - 0.43, p = 0.04, respectively). At 12 months post-CI, the shift in 250 Hz threshold negatively correlated to the variations in VOR gain of superior semicircular canal (SSC) (r = - 0.43, p = 0.04); the HP positively correlated to the variation in oVEMP-amplitude ratio (AR) (r = 0.41, p = 0.04). CONCLUSION: Our study confirmed that there were partial correlations between VF preservation and HP both in the short- and long-terms after atraumatic CI surgery, especially with the 250 Hz threshold. Regarding the variation of PSC function, the correlation with hearing status was variable with time after atraumatic CI surgery. Minimally invasive techniques for HP are successful and effective for the preservation of VF in pediatric patients both in the short- and long-terms.

Effect of Late-Stage Meniere's Disease and Vestibular Functional Impairment on Hippocampal Atrophy.

OBJECTIVE: We investigated correlations among clinical features, degree of inner ear endolymphatic hydrops (EH), and hippocampal volume (HV) in different stages of Meniere's disease (MD). METHODS: From February 2021 to April 2022, clinical data were collected from 99 patients (39 males, 60 females, mean age: 50.4 ± 10.0 [range: 26-69] years) with unilateral MD admitted to the Department of Vertigo Disease of Shandong ENT Hospital. The left and right ears were affected in 64 and 35 patients, respectively. There were 50 and 49 cases in early (Stages 1, 2) and late stages (Stages 3, 4), respectively. Fifty healthy participants were included as controls. Audiovestibular function test results, EH grading using gadolinium-enhanced magnetic resonance imaging (MRI), and HV determined on MRI were analyzed for patients at different stages of MD. RESULTS: Between-group comparisons of early and late MD revealed significant differences in the disease course, vestibular function (VF), degree of EH, and HV. There were no significant between-group differences based on age, sex, affected side, subjective degree of dizziness, hospital anxiety, or depression. Mean HV in patients with early-stage MD was correlated with the canal paresis value of the caloric test and pure tone hearing threshold, HV in late-stage patients was correlated with vestibular EH. CONCLUSION: Patients with late-stage MD exhibited severe auditory and VF impairments, increased EH, and atrophy of the HV. More advanced disease was associated with greater vestibular damage and degree of EH. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:410-418, 2024.

Ménière's disease and allergy: Epidemiology, pathogenesis, and therapy.

The etiology of Ménière's disease (MD) remains controversial. Allergies are potential extrinsic factors that, in conjunction with underlying intrinsic factors, may cause MD. The link between allergies and MD was first described in 1923. For nearly a century, studies have demonstrated a possible link between allergies and MD, even though a causal relationship has not been definitively determined. Previous reviews have mainly focused on clinical epidemiology studies of patients. In this review, we shed light on the association between allergies and MD not only in terms of its epidemiology, but also from an immunology, pathophysiology, and immunotherapy perspective in both patients and animal models. Patients with MD tend to have a high risk of comorbid allergies or an allergy history, showing positive allergy immunology characteristics. Other MD-related diseases, such as migraine, may also interact with allergies. Allergy mediators such as IgE may worsen the symptoms of MD. Deposits of IgE in the vestibular end organs indicate the ability of the inner ear to participate in immune reactions. Allergic challenges can induce vertigo in animals and humans. Anti-allergy therapy plays a positive role in patients with MD and animal models of endolymphatic hydrops.

Triple Semicircular Canal Plugging versus Labyrinthectomy for Meniere Disease: A Retrospective Study.

OBJECTIVES: The study goals were to compare the long-term efficacy of semicircular canal plugging (SCP) with labyrinthectomy in the treatment of advanced Meniere's disease (MD). STUDY DESIGN: A retrospective study. SETTING: Single tertiary medical center. METHODS: A total of 116 MD patients (TSCP group of 90; labyrinthectomy group of 26) with complete medical documents in Shandong Provincial ENT Hospital, from March 2017 to March 2019 were retrospectively analyzed, including a battery of auditory and vestibular function tests, recovery time from imbalance and function level scores (FLS). RESULTS: The total control rate of vertigo in the TSCP group was 96.7% (87/90). The rate of hearing loss was 23.3% (21/90). The control rate of vertigo in the labyrinthectomy group was 100% (26/26). All patients lost their auditory function after labyrinthectomy with a 100% hearing loss rate. There was no significant difference in the vertigo control rate between the two groups (P > 0.05). The hearing loss rate in the TSCP group was significantly lower than that in the labyrinthectomy group (P < 0.00). The median time recovered from imbalance was 15 days in TSCP group and 21 days in labyrinthectomy group, which is significantly different (P < 0.05). There was no significant difference in the FLS between the two groups (P > 0.05). CONCLUSIONS: Compared to labyrinthectomy, TSCP can preserve hearing at a high probability; meanwhile, otolith organ function preservation benefits patients from faster vestibular compensation. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3178-3184, 2023.

Serum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model.

Ménière's disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in Ménière's disease has been proposed, the precise mechanisms remain undefined. Here, we show that downregulation of serum/glucocorticoid-inducible kinase 1 is associated with activation of NLRP3 inflammasome in vestibular-resident macrophage-like cells from Ménière's disease patients. Serum/glucocorticoid-inducible kinase 1 depletion markedly enhances IL-1ß production which leads to the damage of inner ear hair cells and vestibular nerve. Mechanistically, serum/glucocorticoid-inducible kinase 1 binds to the PYD domain of NLRP3 and phosphorylates it at Serine 5, thereby interfering inflammasome assembly. Sgk-/- mice show aggravated audiovestibular symptoms and enhanced inflammasome activation in lipopolysaccharide-induced endolymphatic hydrops model, which is ameliorated by blocking NLRP3. Pharmacological inhibition of serum/glucocorticoid-inducible kinase 1 increases the disease severity in vivo. Our studies demonstrate that serum/glucocorticoid-inducible kinase 1 functions as a physiologic inhibitor of NLRP3 inflammasome activation and maintains inner ear immune homeostasis, reciprocally participating in models of Ménière's disease pathogenesis.

Vestibule Plugging for Patient with Isolated Otolith Dysfunction: A Case Report.

There is currently no satisfactory treatment for otolith dysfunctions. Here, we propose a novel surgical method, vestibule plugging (VP), and the results confirm its effectiveness and safety in treatment of otolith dysfunction. Laryngoscope, 133:1734-1736, 2023.

Long-term efficacy of dexamethasone treatment via tympanic antrum catheterization for intractable Meniere's disease.

Objective: To explore the long-term efficacy and safety of dexamethasone treatment via tympanic antrum catheterization (TAC) in intractable Meniere's disease (MD). Methods: In this retrospective analysis, 60 unilateral intractable MD patients treated with TAC in our hospital from January 2020 to August 2020 were followed for 2 years. Fifty patients who underwent endolymphatic sac decompression (ESD) and 50 patients who accepted intratympanic steroids (ITS) were established as the control groups. Vertigo control, hearing level, tinnitus, aural fullness and functional level were assessed during the study. Results: The effective vertigo control rate of intractable MD patients with TAC treatment was 76.7% (46/60) after 2 years follow-up, with a complete control rate of 58.3% (35/60) and a substantial control rate of 18.3% (11/60). The vertigo control rate of TAC was comparable to that of ESD (χ 2 = 0.313, p > 0.05), and significantly higher than that of ITS (χ 2 = 4.380, p < 0.05). The hearing loss rate of these patients was 10.8% (4/37), which was not significantly different from the control groups (χ 2 = 2.452, p > 0.05). The tinnitus improvement rate of patients with TAC was 56.7% (34/60), which was significantly higher than that of patients with ESD (χ 2 =11.962, p < 0.001) and ITS (χ 2 =15.278, p < 0.001). The aural fullness improvement rate in the TAC group was 56.7% (34/60), which was significantly higher than that in the ESD (χ 2 = 11.962, p < 0.001) and ITS groups (χ 2 = 5.635, p < 0.05). The functional level improvement rate in the TAC group was 71.7% (43/60), which was much higher than that in the ITS group (χ 2 = 17.256, p < 0.001), but there was no significant difference between TAC and ESD (χ 2 = 0.410, p > 0.05). No patients had complications or adverse reactions following TAC treatment. Conclusion: Dexamethasone treatment via TAC can effectively control vertigo attacks and improve related symptoms of intractable MD patients, providing valuable new insights into the treatment of MD.

Sensory organization of balance control in children with vestibular migraine and recurrent vertigo of childhood.

Background: Migraine plays an important role in some subgroups of children with recurrent vertigo. Moreover, the migraine component varies from definite to possibly absent as defined in this spectrum of three disorders-vestibular migraine of childhood (VMC), probable VMC (pVMC), and recurrent vertigo of childhood (RVC). However, studies on the sensory organization of balance control in these three disorders are rare. Objective: To explore the balance control of children with RVC, VMC, and pVMC, when the three sensory systems are challenged. Method: A retrospective analysis was performed on 125 children with VMC (18 female and 15 male; aged 11.64 ± 2.74), pVMC (10 female and eight male; aged 11.78 ± 2.51), and RVC (32 female and 42 male; aged 11.10 ± 2.60). All children in each subtype were divided into groups of children aged ≤ 12 years old and 13-17 years old. Vestibular examination screening and assessment for postural control using the six conditions of the sensory organization test (SOT) were performed. The three primary outcome measures were: equilibrium score (ES), strategy score (SS), and sensory analysis score of the SOT. Results: Equilibrium score under six different conditions and composite score increased with age (all P-values < 0.05). The somatosensory and visual scores also improved with growing (P-values < 0.05). However, vestibular scores did not increase significantly with age as the other senses did (P > 0.05). In the children ≤ 12 year-old group, children with VMC had a significantly higher visual preference score than those with pVMC and RVC (P < 0.05). There was an effect of age on the horizontal HIT. Ocular vestibular evoked myogenic potential (oVEMP), cervical vestibular evoked myogenic potential (cVEMP), and unilateral weakness (UW) values showed no significant difference among three diseases. Conclusion: Compared with patients at the age of 13-17 years old and with RVC and pVMC (both ≤ 12 years old), children with VMC had a higher degree of reliance on visual signals to maintain their balance and a poorer central integration of peripheral information before reaching 12 years of age. In addition, vision may predominate by weakening vestibular function based on visuo-vestibular interactions. It must be noted that peripheral vestibular examinations could not distinguish the three disease subtypes.

Efficacy of Resection of Lateral Wall of Endolymphatic Sac for Treatment of Meniere's Disease.

Background: To explore the long-term efficacy and safety of resection of the lateral wall of the endolymphatic sac for the treatment of intractable Meniere's disease (MD) as an alternative surgical procedure for treating this disorder. Methods: Data from 73 patients who were referred to our hospital and diagnosed with unilateral MD between January 2015 and June 2019 were retrospectively analyzed in this study. Seventy-three patients who had frequent vertigo even after receiving standardized conservative treatment for at least half a year underwent resection of the lateral wall of the endolymphatic sac. Vertigo control and auditory function were assessed. Pure tone audiometry, caloric test, and vestibular evoked myogenic potential were performed to evaluate audiological and vestibular functions. The post-operative follow-up duration was more than 2 years. Results: Among the 73 patients (male 34 cases, female 39 cases; age 20-69 years, average 51.4), vertigo was controlled effectively for 66 cases (90.4%) after 2 years of follow-up; 45 cases (61.6%) were completely controlled, and 21 cases (28.8%) were substantially controlled in this study. The patients of 16.4% had hearing loss with more than 10 dB change based on the four-tone average (0.5, 1, 2 and 3 kHz). No patient had a facial nerve weakness, cerebrospinal fluid leakage, or other complications. Conclusion: Resection of the lateral wall of the endolymphatic sac, which can effectively control vertiginous symptoms in intractable MD patients, represents an effective and safe therapy for this disease. Resection of the lateral wall of the endolymphatic sac is expected to be used as an alternative treatment for MD.

The Alterations and Significance of Intercellular Adhesion Molecule-1 in Mouse Brainstem During Herpes Simplex Virus Type 1-Induced Facial Palsy.

Herpes simplex virus type 1 (HSV-1) results in the development of Bell's pals but still, the pathophysiology of the facial nerve paralysis is still not fully studied. The main objective is to establish an animal model of type 1 herpes simplex virus (HSV-1)-induced face paralysis in the mouse and to investigate the pattern of changes in intercellular adhesion molecule -1(ICAM-1) expression in the facial nucleus of the brain stem in mice with facial paralysis as well as the effects of glucocorticoids on intercellular adhesion molecule -1(ICAM-1) expression. A total of 170 4-week-old Balb/c male mice were randomly divided into the virus inoculation group (n = 135), saline control group (n = 26), and blank control group (n = 9). Mice in the virus inoculation group that showed facial paralysis were divided into A, B, and C subgroups. The A group did not receive any treatments, the B group received methylprednisolone sodium succinate (MPSS) intervention, and the C group received MPSS + RU486 treatment. The mouse model of facial paralysis was established by inoculating HSV-1 to the skin at the back of the ears. The facial nerve function of mice was assessed, and real-time PCR and western blot were used to assess ICAM-1 expression in the facial nucleus of the brain stem in mice with facial paralysis after drug intervention. In the virus inoculation group, 95 mice (55.88%) showed varying degrees of facial paralysis symptoms within 2-5 days after inoculation. The ICAM-1 gene and protein expression levels remained at low levels in the facial nucleus of the brain stem of mice in the saline group, which showed no significant difference compared to the normal control group (P > 0.05). However, for mice of the virus inoculation group, ICAM-1 expression increased at 6 h after the occurrence of facial paralysis and peaked after 2 days, differing significantly from the blank control group (P < 0.01). ICAM-1 expression subsequently decreased gradually. In the HSV-1 + MPSS group, ICAM-1 protein expression decreased significantly on the 2nd day after facial paralysis. In the HSV-1 + MPSS + RU486 group, MPSS inhibition of ICAM-1 protein expression was reduced. The results suggested that ICAM-1 is involved in the pathological processes by which HSV-1 induces facial paralysis in mice, and the treatment effects of MPSS for Bell's palsy can be achieved by the inhibition of MCP-1.

Idiopathic Sudden Sensorineural Hearing Loss in Different Ages: Prognosis of Patients With Initial Total Hearing Loss.

Objective: This study aimed to analyze the hearing improvement and prognosis factors of idiopathic sudden sensorineural hearing loss (ISSNHL) in different ages with initial total hearing loss. Methods: We reviewed the medical records of 5,711 hospitalized patients with ISSNHL from 2016 to 2021 in our center. All of the patients had been treated with uniform combination drug therapy. After excluding the patients with initial partial hearing loss and those diagnosed with clear etiology, 188 patients were enrolled in this study and divided into six age groups (18-30, 31-40, 41-50, 51-60, 61-70, ≥ 71 years). In all groups, decreases in pure-tone average (PTA) 1 month posttreatment, effective rate, and clinical characteristics (vertigo, tinnitus, hospital stay, comorbidity, and inner ear magnetic resonance imaging) were analyzed. Results: Among the 188 enrolled patients, 86% had vertigo. Complete recovery was seen in 0.5% of patients, and marked recovery was seen in 43% of patients. The mean 1 month posttreatment PTAs were as follows: 18-30 years: 80 ± 7.5 dB; 31-40 years: 100 ± 9.0 dB; 41-50 years: 99 ± 8.3 dB; 51-60 years: 101 ± 8.6 dB; 61-70 years: 96 ± 9.6 dB; and ≥ 71 years: 88 ± 13.0 dB. Compared with the other groups, the 18-30- years group showed better recovery of hearing threshold in five frequencies (0.25, 0.5, 1, 2, and 4 kHz, respectively, at octave or semioctave frequencies under air conduction), and the recovery of hearing threshold at 0.25 and 0.5 Hz was better than the recovery at 1, 2, and 4 kHz. According to the results of the chi-square test statistical analysis, vertigo and comorbidities were associated with a poor prognosis of ISSNHL. Conclusion: In summary, the treatment outcomes of patients with ISSNHL with initial total hearing loss were poor. There was a significant age-related difference with respect to marked recovery 1 month posttreatment, and the 18-30- years group showed better recovery than the other age groups.

Bidirectional Transport of IgE by CD23 in the Inner Ear of Patients with Meniere's Disease.

Meniere's disease (MD) is a disorder of the inner ear characterized by episodes of spontaneous vertigo, fluctuating hearing loss, and tinnitus. Recent studies have demonstrated that IgE may play a role in the pathogenesis of MD. Patients with MD (n = 103), acoustic neuroma (n = 5), and healthy subjects (n = 72) were recruited into the study. Serum from the participants was analyzed for IgE and type 2-related cytokines. IgE and CD23 expression levels in vestibular end organs of patients, C57BL/6 mice, or mouse HEI-OC1 cells were analyzed. Finally, the role of CD23 in IgE transcytosis was assessed using HEI-OC1 cells. Serum IgE was elevated in patients with MD and positively correlated with clinical symptoms. IL-4, IL-5, IL-10, IL-13, and CD23 levels were increased in patients with MD compared with the control group. In the transcytosis assay, mouse IgE was found to be bidirectionally transported across the HEI-OC1 cell monolayer. Additionally, CD23 downregulation using a small interfering RNA approach significantly reduced the efficiency of IgE transcytosis, suggesting that IgE is transported by CD23. Furthermore, exposure to IL-4 increased CD23 expression and enhanced IgE transcytosis in the HEI-OC1 cells and primary vestibular end organs. Our study indicated that IgE may play a role in the pathophysiology of MD. In addition, CD23-mediated IgE transcytosis in the hair cells may play a critical role in initiating inflammation in the inner ear. Thus, reducing the level of IgE may be a potentially effective approach for MD treatment.

Protective effect of anakinra on audiovestibular function in a murine model of endolymphatic hydrops.

Introduction: Ménière's disease (MD), a common disease in the inner ear, is characterized by an increase in endolymph in the cochlear duct and vestibular labyrinth. The pathophysiology of the condition appears to be the immune response. Studies have shown that basal levels of the IL-1ß increased in some MD patients. Methods: Here, we used a murine model of endolymphatic hydrops (EH) to study the effect of anakinra on auditory and vestibular function. Mice were intraperitoneal injected with anakinra or saline before LPS by postauricular injection. Weight and disease severity were measured, histologic changes in auditory were assessed, and inflammation state was evaluated. Results: We found that anakinra therapy reduced LPS-induced EH, alleviated LPS-induced hearing loss and vestibular dysfunction, and inhibited the expression of the inflammatory cytokines and macrophage infiltration in the cochlea of mice. We further demonstrated that anakinra ameliorated the disorganization and degeneration of myelin sheath, and reduced the neuron damage in cochlea of EH mice. Discussion: Consequently, anakinra contributes to a promising therapeutic approach to MD, by restricting EH, alleviating auditory and vestibular function, inhibiting inflammation of the inner ear and protecting the cochlear nerve. Further investigations are needed to assess the potential therapeutic benefits of anakinra in patients with MD.

Objective vestibular function changes in children following cochlear implantation.

BACKGROUND: To date, systematically objective evaluations of vestibular function in children with cochlear implantation (CI) have been conducted sparsely, especially in children with large vestibular aqueduct syndrome (LVAS). OBJECTIVE: Our goal was to investigate the function of all five vestibular end-organs pre- and post-cochlear implantation in children with LVAS and normal CT. METHODS: In this retrospective cohort study, 34 children (age 4-17 years) with bilateral profound sensorineural hearing loss (SNHL) undergoing unilateral CI were included. Participants included 18 (52.9%) children with LVAS. Objective modalities to evaluate vestibular function included the caloric test, cervical vestibular-evoked myogenic potentials (cVEMP), ocular vestibular-evoked myogenic potentials (oVEMP), and video head impulse test (vHIT). All measurements were performed before surgery and 9 months after surgery. RESULTS: Mean age at CI was 8.1±3.7 years. Caloric testing showed hypofunction in 38.2% of cases before implantation and in 50% after (p > 0.05). We found a significant increase of overall abnormality rate in cVEMP and oVEMP from pre- to post-CI (p < 0.05). In all three semicircular canals tested by vHIT, there were no statistically significant mean gain changes (p > 0.05). Higher deterioration rates in cVEMP (53.3%) and oVEMP (52.0%) after surgery were observed (p < 0.05). In children with LVAS, cVEMP revealed a higher deterioration rate than superior semicircular canal (SSC) and posterior semicircular canal (PSC) (p < 0.05). In children with normal CT, the deterioration rates in VEMPs were both higher than those in vHIT (p < 0.05). CONCLUSIONS: In general, the otolith organs were the most affected peripheral vestibular sensors in children after cochlear implantation. The variations in otolith function influenced by CI were different between children with LVAS and normal CT. We recommend the use of this vestibular function test battery for children with cochlear implantation.

Sperm-associated antigen 6 (Spag6) mutation leads to vestibular dysfunction in mice.

Spag6 encodes an axoneme central apparatus protein that is required for normal flagellar and cilia motility. Recent findings suggest that Spag6 plays a role in hearing and planar cell polarity (PCP) in the cochlea of the inner ear. However, a role for Spag6 in the vestibule has not yet been explored. In the present study, the function of Spag6 in the vestibule of the inner ear was examined using Spag6-deficient mice. Our results demonstrate a vestibular disorder in the Spag6 mutants, associated with abnormal ultrastructures of vestibular hair cells and Scarpa's ganglion cells, including swollen stereocilia, decreased crista in mitochondria and swollen Scarpa's ganglion cells. Immunostaining data suggests existence of caspase-dependent apoptosis in vestibular sensory epithelium and Scarpa's ganglion cells. Our observations reveal new functions for Spag6 in vestibular function and apoptosis in the mouse vestibule.

Influence of Cochlear Implantation on Vestibular Function in Children With an Enlarged Vestibular Aqueduct.

Background: Cochlear implantation (CI) is becoming increasingly used in the rehabilitation of hearing-impaired patients. Children with an enlarged vestibular aqueduct (EVA) need CI for severe or profound hearing loss, with excellent outcomes in hearing rehabilitation. However, vestibular function influenced by CI in children with EVA has not been clarified. We compared the characteristics of vestibular function in implanted children with EVA and those with a normal cochlea. Methods: In this retrospective case-control study, 16 children with large vestibular aqueduct syndrome (LVAS) and 16 children with a normal cochlea were recruited as the Study and Control Group, respectively. All children (mean age, 10.3 ± 4.4 years) had bilateral profound sensorineural hearing loss (SNHL) and normal pre-operative vestibular functions and underwent unilateral CI. Otolith and canal functions were assessed before CI and 12 months thereafter. Cervical vestibular-evoked myogenic potential (cVEMP), ocular vestibular-evoked myogenic potential (oVEMP), and video head impulse test (vHIT) were evaluated. Results: Full insertion of the electrode array was achieved in all the cases. Preoperatively, no significant differences in parameters in cVEMP between the Study and Control Group were revealed (p > 0.05). In pre-operative oVEMP, shorter N1 latencies (p = 0.012), shorter P1 latencies (p = 0.01), and higher amplitudes (p = 0.001) were found in the Study than in the Control Group. The Study Group had shorter P1 latency in cVEMP (p = 0.033), and had lower amplitude in oVEMP after implantation (p = 0.03). Statistically significant differences were not found in VOR gains of all three semicircular canals before and after surgery (p > 0.05). VEMP results revealed that the Control Group had significantly lower deterioration rates after CI (p < 0.05). The surgical approach and electrode array had no statistically significant influence on the VEMP results (p > 0.05). Conclusion: oVEMP parameters differed between children with EVA and children with a normal cochlea before surgery. Systematic evaluations before and after CI showed that otolith function was affected, but all three semicircular canals functions were essentially undamaged after implantation. In contrast to subjects with a normal cochlea, children with EVA are more likely to preserve their saccular and utricular functions after CI surgery. Possible mechanisms include less pressure-related damage, a reduced effect in terms of the air-bone gap (ABG), or more sensitivity to acoustic stimulation.

PRDX1 activates autophagy via the PTEN-AKT signaling pathway to protect against cisplatin-induced spiral ganglion neuron damage.

Spiral ganglion neurons (SGNs) are auditory neurons that relay sound signals from the inner ear to the brainstem. The ototoxic drug cisplatin can damage SGNs and thus lead to sensorineural hearing loss (SNHL), and there are currently no methods for preventing or treating this. Macroautophagy/autophagy plays a critical role in SGN development, but the effect of autophagy on cisplatin-induced SGN injury is unclear. Here, we first found that autophagic flux was activated in SGNs after cisplatin damage. The SGN apoptosis and related hearing loss induced by cisplatin were alleviated after co-treatment with the autophagy activator rapamycin, whereas these were exacerbated by the autophagy inhibitor 3-methyladenine, indicating that instead of inducing SGN death, autophagy played a neuroprotective role in SGNs treated with cisplatin both in vitro and in vivo. We further demonstrated that autophagy attenuated reactive oxygen species (ROS) accumulation and alleviated cisplatin-induced oxidative stress in SGNs to mediate its protective effects. Notably, the role of the antioxidant enzyme PRDX1 (peroxiredoxin 1) in modulating autophagy in SGNs was first identified. Deficiency in PRDX1 suppressed autophagy and increased SGN loss after cisplatin exposure, while upregulating PRDX1 pharmacologically or by adeno-associated virus activated autophagy and thus inhibited ROS accumulation and apoptosis and attenuated SGN loss induced by cisplatin. Finally, we showed that the underlying mechanism through which PRDX1 triggers autophagy in SGNs was, at least partially, through activation of the PTEN-AKT signaling pathway. These findings suggest potential therapeutic targets for the amelioration of drug-induced SNHL through autophagy activation.Abbreviations: 3-MA: 3-methyladenine; AAV : adeno-associated virus; ABR: auditory brainstem responses; AKT/protein kinase B: thymoma viral proto-oncogene; Baf: bafilomycin A1; CAP: compound action potential; COX4I1: cytochrome c oxidase subunit 4I1; Cys: cysteine; ER: endoplasmic reticulum; H2O2: hydrogen peroxide; HC: hair cell; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; NAC: N-acetylcysteine; PRDX1: peroxiredoxin 1; PTEN: phosphatase and tensin homolog; RAP: rapamycin; ROS: reactive oxygen species; SGNs: spiral ganglion neurons; SNHL: sensorineural hearing loss; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling; WT: wild type.

Long-term efficacy of triple semicircular canal plugging in the treatment of patients with ipsilateral delayed endolymphatic hydrops.

This study aims to explore the long-term efficacy of triple semicircular canal plugging (TSCP) in the treatment of intractable ipsilateral delayed endolymphatic hydrops (DEH), so as to provide an alternative therapy for this disease. Forty-eight patients diagnosed with ipsilateral DEH referred to vertigo clinic of our hospital between Dec. 2010 and Dec. 2017, were included in this study for retrospective analysis. All patients were followed up for 2 years. Vertigo control and auditory functions were measured and analyzed. Pure tone audiometry, caloric test, and vestibular evoked myogenic potential (VEMP) were performed in two-year follow-up. Forty-five patients who accepted intratympanic gentamicin (26.7 mg/mL) twice given one week apart were selected as a control group. The total control rate of vertigo in TSCP group was 97.9% (47/48) in the two-year follow-up, with complete control rate of 83.3% (40/48) and substantial control rate of 14.6% (7/48). The rate of hearing loss was 22.9% (11/48). The total control rate of vertigo in intratympanic gentamicin group was 80.0% (36/45), with complete control rate of 57.8% (26/45) and substantial control rate of 22.2% (10/45), and the rate of hearing loss was 20.0% (9/45). The vertigo control rate of TSCP was significantly higher than that of intratympanic gentamicin (χ2 = 6.01, p < 0.05). There was no significant difference of hearing loss rate between two groups. (χ2 = 0.12, p > 0.05). TSCP, which can reduce vertiginous symptoms in patients with intractable ipsilateral DEH, represents an effective therapy for this disorder.

Characterization of EGR-1 Expression in the Auditory Cortex Following Kanamycin-Induced Hearing Loss in Mice.

Deprivation of acoustic input during a critical period leads to abnormal auditory development in humans. The molecular basis underlying the susceptibility of auditory cortex to loss of afferent input remains largely unknown. The transcription factor early growth response-1 (EGR-1) expression in the visual cortex has been shown to be crucial in the formation of vision, but the role of EGR-1 during the process of auditory function formation is still unclear. In this study, we presented data showing that EGR-1 was expressed in the neurons of the primary auditory cortex (A1) in mice. We observed that the auditory deprivation induced by kanamycin during the auditory critical period leads to laminar-specific alteration of neuronal distribution and EGR-1 expression in A1. In addition, MK-801 administration inhibited the expression of EGR-1 in A1 and aggravated the abnormal cortical electric response caused by kanamycin injection. Finally, we showed that the expression of PI3K, the phosphorylation of Akt, as well as the phosphorylation of cAMP-responsive element-binding protein (CREB) were decreased in A1 after kanamycin-induced hearing loss. These results characterized the expression of EGR-1 in A1 in response to the acoustic input and suggested the involvement of EGR-1 in auditory function formation.