Bilateral vestibular hypofunction (BVH) is a chronic disorder in which the balance organs or vestibular pathways on both sides do not work normally. People with BVH may experience unsteadiness, blurred or unstable vision during head movement, difficulty walking, and an increased risk of falls. At present, there are limited targeted medical treatments, and the reasons why symptoms are severe in some patients but mild in others are not fully understood.

This prospective, multicenter, cross-sectional study will investigate the relationships among vestibular function, brain structure and function, blood biomarkers, patient-reported symptoms, and disease severity in people with BVH. The study will enroll approximately 120 participants from five medical centers in China, including about 80 patients with BVH and 40 age-matched healthy controls.

Participants will undergo vestibular function tests, including videonystagmography, caloric testing, sinusoidal harmonic acceleration testing, video head impulse testing, vestibular evoked myogenic potentials, and sensory organization testing. Brain imaging will include resting-state functional magnetic resonance imaging, diffusion tensor imaging, and diffusion kurtosis imaging. Participants will also complete questionnaires related to dizziness, anxiety and depression, daily activities, and symptom severity, and blood samples will be collected for biochemical and inflammatory marker testing.

The main hypothesis is that BVH severity is associated with measurable changes in vestibular function, brain functional connectivity and microstructure, inflammatory or metabolic biomarkers, and patient-reported quality of life. By combining clinical testing, neuroimaging, laboratory measures, and symptom scales, this study aims to improve understanding of the mechanisms of BVH and to support future development of more individualized diagnostic and rehabilitation strategies.

This is a prospective, multicenter, cross-sectional observational study designed to investigate the clinical, vestibular, neuroimaging, biochemical, and patient-reported characteristics associated with bilateral vestibular hypofunction (BVH). The study will recruit patients with BVH and age-matched healthy controls from five medical centers in China. The planned total sample size is approximately 120 participants, including about 80 patients with BVH and 40 healthy controls.

The main objective of the study is to clarify the relationships among vestibular function, brain structure and function, biochemical variables, patient-reported symptoms, quality of life, and the severity of BVH. The study will also examine patterns of brain activity, functional connectivity, and diffusion-related microstructural changes using resting-state functional magnetic resonance imaging (rs-fMRI), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DKI). By integrating these assessments, the study aims to identify clinical and biological factors that may be associated with disease severity and functional impairment in BVH.

After providing written informed consent, eligible participants will undergo collection of demographic and clinical information, including age, sex, education, blood pressure, height, weight, and medical history. Participants will then complete a series of vestibular function assessments, neuroimaging examinations, clinical symptom scales, and laboratory tests. The study is observational and cross-sectional; no investigational drug, device, surgical procedure, or therapeutic intervention will be assigned as part of the study.

Vestibular function will be assessed using several complementary tests. Videonystagmography will be used to record and evaluate eye movements, including spontaneous nystagmus, gaze, saccade, and smooth pursuit eye movements. Caloric testing will be used to evaluate bilateral vestibular responsiveness and symmetry. Sinusoidal harmonic acceleration testing will assess vestibulo-ocular reflex performance during rotational stimulation. Video head impulse testing will assess dynamic semicircular canal function. Vestibular evoked myogenic potentials will be used to evaluate otolith-related vestibular function, and sensory organization testing will assess balance control under different sensory conditions.

Neuroimaging will include anatomical magnetic resonance imaging, resting-state functional magnetic resonance imaging, diffusion tensor imaging, and diffusion kurtosis imaging. During magnetic resonance imaging, participants will be instructed to remain still, relax, breathe steadily, keep their eyes closed while remaining awake, and avoid intentional cognitive tasks. Anatomical imaging will be used to screen for intracranial structural abnormalities. Resting-state functional magnetic resonance imaging will be used to examine spontaneous brain activity and functional connectivity. Diffusion tensor imaging and diffusion kurtosis imaging will be used to assess white matter integrity and microstructural tissue features.

Patient-reported assessments will include standardized scales evaluating dizziness-related disability, anxiety and depression symptoms, dizziness severity, and the impact of vestibular symptoms on activities of daily living. These assessments will include the Dizziness Handicap Inventory, Hospital Anxiety and Depression Scale, Visual Analog Scale, and Vestibular Disorders Activities of Daily Living Scale.

Laboratory assessments will include biochemical, metabolic, inflammatory, and anti-inflammatory markers. These measures will include lipid-related indicators, glucose metabolism-related indicators, liver and renal function-related indicators, inflammatory biomarkers, anti-inflammatory biomarkers and apolipoprotein E genotyping, according to the study protocol.

The primary analyses will focus on the relationships between BVH and multimodal objective measures, including neuroimaging indicators and vestibular function test results. Secondary analyses will evaluate associations involving patient-reported scales and laboratory variables. Neuroimaging data will be processed using established software platforms for functional and diffusion imaging analysis. Statistical analyses will be used to compare patients and controls and to explore associations between vestibular function, neuroimaging measures, laboratory biomarkers, symptom burden, and BVH severity.

Participant safety will be monitored throughout the study. Participants may withdraw or be withdrawn from the study if they experience an allergic reaction, a serious adverse event, or another condition judged by the investigators to make continued participation unsuitable. The study has received ethics approval from the Ethics Committee of Shanghai Sixth People's Hospital and will be conducted in accordance with applicable ethical requirements. Written informed consent will be obtained before enrollment.

Inclusion Criteria:

1. Sex unrestricted, age over 16 years old.
2. Patients meeting the diagnostic criteria for bilateral vestibulopathy (BVP) and presbyvestibulopathy (PVP)
3. Participants or their legal representatives, who comprehensively understand the research purpose, demonstrate sufficient compliance with the study protocol, have the ability to communicate and cooperate, and have signed the informed consent form.

Exclusion Criteria:

1. Administration of medications potentially affecting cerebral function, including psychotropic drugs (antidepressants, anxiolytics) or prolonged anti-vertigo medication usage.
2. Presence of severe cardiovascular or systemic medical conditions, organ dysfunction, or significant mobility impairments.
3. Significant local or systemic diseases, or psychiatric disorders causing cognitive impairment, specifically schizophrenia, major depressive disorder, or generalized anxiety disorder.
4. Pregnant or lactating women.
5. Participation in alternative pharmaceutical or medical device clinical trials within the preceding 3-month period.
6. Clinically significant head movement restrictions.
7. Subjects assessed by investigators as unsuitable for study participation.
8. Individuals with contraindications for MRI, including cardiac pacemakers, implanted electronic devices, claustrophobia, metallic implants incompatible with magnetic resonance imaging and medications potentially compromising MRI scan safety.

The study population will consist of participants aged over 16 years, including patients diagnosed with bilateral vestibular hypofunction (BVH) and age-matched healthy controls. Patients with BVH will include individuals meeting the diagnostic criteria for bilateral vestibulopathy (BVP) or presbyvestibulopathy (PVP). A total of 120 participants will be enrolled from five medical centers, including 80 BVH patients and 40 healthy controls. All participants must be able to understand the study procedures, comply with the protocol, communicate and cooperate with investigators, and provide written informed consent.

De-identified individual participant data underlying the published results may be shared with qualified researchers upon reasonable request after publication of the main study results, subject to approval by the relevant ethics committee and execution of a data access agreement. Shared data may include clinical scale scores, vestibular function test results, laboratory variables, and processed neuroimaging-derived measures. Direct identifiers and raw imaging data will not be shared unless specifically approved by the ethics committee.

De-identified IPD and supporting information will become available beginning 1 year after publication of the main study results and will remain available for 5 years following publication.

Access will be granted to qualified researchers who submit a methodologically sound research proposal for scientific purposes related to bilateral vestibular hypofunction, vestibular disorders, neuroimaging, or related clinical research. Requests will be reviewed by the principal investigator and the relevant ethics committee. Data will be shared only after approval of the request and execution of a data access agreement. Shared data may include de-identified clinical scale scores, vestibular function test results, laboratory variables, and processed neuroimaging-derived measures. Direct identifiers and raw imaging data will not be shared unless specifically approved by the ethics committee.