Hereditary hearing loss is the most common sensory disorder in humans, affecting roughly 1 in 500 newborns and accounting for more than half of congenital deafness. Although over 200 deafness-associated genes have been identified, effective treatments remain scarce. Adeno-associated virus (AAV)-mediated gene therapy has rapidly advanced from proof-of-concept studies in animal models to early clinical evidence of hearing restoration in humans. Here, we review recent progress in AAV vector development, including natural and engineered serotypes, strategies for packaging large genes, and innovations in cochlear delivery. We also summarize insights emerging from global clinical trials, which collectively demonstrate that precise cochlear targeting with AAV vectors can restore auditory function across a broad age range. These advances mark a decisive transition for the field—from experimental exploration to a clinically actionable framework—and position AAV-mediated gene therapy as a promising therapeutic paradigm for hereditary hearing loss.
Background: : The submental island flap (SIF) is valuable for head and neck reconstruction, but anatomical variations in submental vasculature pose surgical challenges. Systematic preoperative imaging may optimize planning and minimize vascular injury.
Objective: : To develop a standardized CT-based protocol for preoperative assessment of submental flap vasculature and characterize common anatomical patterns.
Methods: : Contrast-enhanced CT images from 109 patients (218 sides) were retrospectively analyzed between January and June 2024. A systematic protocol identified submental artery origin, traced its course relative to mylohyoid and digastric muscles, and determined facial vein drainage patterns using Fang's classification (Type I: internal jugular vein; Type II: external jugular vein; Type III: anterior jugular vein).
Results: : The submental artery origin was consistently identified within the "submental artery triangle" bounded by the mandible, mylohyoid muscle, and submandibular gland. The main trunk coursed deep to the digastric muscle in 31.1%, superficial in 33.0%, and penetrating through in 35.9%. Facial vein drainage patterns included Type I (56.3%), Type II (32.5%), and Type III (11.2%), with significant gender differences observed (p < 0.001).
Conclusion: : This standardized CT protocol enables reliable preoperative prediction of submental flap vascular anatomy, facilitating surgical planning and reducing risk of inadvertent vascular injury during flap harvest.
Background:: This study aimed to investigate the potential role of binocular video head impulse test (B-vHIT) in distinguishing non-peripheral and peripheral vertigo.
Methods:: A cohort of 46 healthy volunteers underwent B-vHIT to establish normative reference values. Concurrently, 104 patients presenting with acute vertigo (onset ≤ 72 hours) underwent B-vHIT and HINTS protocol. B-vHIT parameters were analyzed according to imaging-supported clinical diagnoses and compared with HINTS results. Further, a four-category framework was proposed to differentiate non-peripheral from peripheral vertigo.
Results:: Significant differences in Interocular Gain Asymmetry (χ2 = 68.381, P < 0.001) and Interocular Gain Difference (χ2 = 50.187, P < 0.001) were observed among groups, revealing a post-hoc hierarchical pattern in which peripheral ophthalmoplegic-related dizziness (POD) group had the highest values, followed by central vertigo, peripheral vertigo and healthy controls. An Asymmetry threshold of < 16 combined with a Difference threshold of < 0.2 achieved 86.4% sensitivity and 89.2% specificity in distinguishing non-peripheral from peripheral causes of vertigo. The Type I (Gain−, Difference−) and Type IV (Gain+, Difference+) patterns demonstrated high specificity (99%) and sensitivity (79%) for identifying non-peripheral vertigo.
Conclusion:: The B-vHIT can serve as a useful tool to distinguish between two types vertigo. The classification framework integrating Gain and Difference should be further investigated for distinguishing non-peripheral vertigo from peripheral vertigo.
Background: : This study aimed to investigate whether neurovascular compression (NVC) between the anterior inferior cerebellar artery (AICA) and the vestibulocochlear nerve (CVN) in the cerebellopontine angle (CPA) contributes to the pathophysiological differences between vestibular neuritis (VN) and Ramsay Hunt syndrome with dizziness (RHSD), both of which are recognized as vestibular disorders potentially resulting from viral reactivation.
Methods: : Twenty-two VN patients and 10 RHSD patients were included. The AICAs of these patients were assessed using Chavda, Gorrie, and Kazawa classification systems based on magnetic resonance imaging (MRI) findings of the CPA. All patients also underwent pure-tone audiometry (PTA), caloric test, and video head impulse test (vHIT).
Results: : (1) In VN patients, AICA types classified by Kazawa system showed a significant difference between the affected and non-affected sides (p = 0.011). (2) There was no significant difference in AICA types classified by all three systems on the affected side between VN and RHSD patients. (3) In RHSD patients, the AICA types classified by Gorrie system on the affected side were significantly associated with PTA (p = 0.016).
Conclusions: : While NVC appears to play a limited role in the differential pathophysiologic mechanisms of VN and RHSD, its contribution to peripheral vestibulopathy warrants further investigation.
Background: : Emerging evidence highlights the vestibular system's critical role in cognitive function, though the mechanisms linking vestibular dysfunction to cognitive decline remain unclear, necessitating further large-scale studies. This study aimed to analyze the relationship between vestibular function and cognitive impairment in older adults.
Methods: : We assessed the impact of vestibular function on cognitive performance in rural older adults aged 60 and above (n = 479) using data of the 2024 Taizhou Imaging Study Cohort. Vestibular function was measured using the modified Romberg test and self-designed balance questionnaire, while cognitive function was assessed with the MMSE and MoCA scale. Diagnosis of dementia and mild cognitive impairment (MCI) was based on comprehensive cognitive assessments. Correlation analyses and multivariable unconditional logistic regression were performed to evaluate the relationship between vestibular function and cognitive performance.
Results: : The average age of the study population was 67.73 years (SD = 3.9). The prevalence of dementia was 7.5%, and the prevalence of mild cognitive impairment was 26.7%. Vestibular dysfunction, as assessed by the modified Romberg test, had a prevalence of 11.4%, while the prevalence of subjective vestibular dysfunction, based on self-reported symptoms from the balance questionnaire, was 19%. The self-reported rate of dizziness was significantly higher in females (24%) compared to males (12.7%) (p = 0.003). Correlation analysis revealed a significant positive correlation between vestibular function and cognitive function (Montreal Cognitive Assessment [MoCA]: r = 0.16, p < 0.05; Mini-Mental State Examination [MMSE]: r = 0.19, p < 0.05). However, logistic regression analysis indicated that vestibular dysfunction was not a significant factor influencing dementia prevalence, while education level and hearing status were identified as protective factors for cognitive function.
Conclusions: : Our study reveals a high prevalence of both vestibular dysfunction and cognitive impairment among the elderly in rural China. While there is a significant correlation between vestibular function and cognitive performance, multivariable analysis failed to identify vestibular dysfunction as an independent risk factor for dementia. This suggests that vestibular function may influence overall cognitive abilities but does not directly drive the onset of dementia. Future research is warranted to elucidate the specific mechanisms linking vestibular health to cognitive decline.
Background: : Gene therapy for deafness requires adeno-associated virus (AAV) vectors with enhanced efficiency and cell-type specificity within the inner ear. However, the limited tropism of existing AAV serotypes remains a major barrier to precise cochlear gene delivery in adult subjects.
Methods: : An AAV1 capsid library containing randomized nine–amino acid peptide insertions at position 588 within the variable region VIII (VR-VIII) was constructed. The library was packaged and subjected to three rounds of in vivo directed evolution via posterior semicircular canal injection into the cochleae of adult (P35–P40) C57BL/6 mice. Selected variants were analyzed by next-generation sequencing. Representative candidates were packaged with an EGFP reporter to evaluate cell-type tropism and auditory safety.
Results: : Next-generation sequencing demonstrated robust selection, with the top variant, WAC19-1, showing nearly a two-million-fold enrichment. Candidate variants exhibited diverse and enhanced cochlear tropism profiles. WAC19-2 achieved highly efficient transduction of hair cells, reaching 100% infection of both inner and outer hair cells across all cochlear turns. WAC19-7 displayed the broadest supporting cell tropism, selectively infecting outer phalangeal cells throughout the cochlea. Auditory function assessment revealed that WAC19-1, WAC19-5, and WAC19-7 did not significantly affect hearing thresholds 14 days after injection. In contrast, WAC19-2 caused mild hearing threshold elevation at 5.6 kHz, while WAC19-3 resulted in severe hearing loss.
Conclusion: : This study identifies a panel of novel AAV variants with distinct and enhanced tropisms for specific cochlear cell populations in the adult mouse inner ear. The findings highlight the importance of balancing transduction efficiency and auditory safety and provide valuable viral tools for precise inner ear gene delivery and future therapeutic development.