Deep Phenotyping of Hearing Instability Disorders: Cohort Establishment, Biomarker Identification, Development of Novel Phenotyping Measures, and Discovery of Therapeutic Targets

• NCLUSION CRITERIA:

Affected Adults

In order to be eligible to participate in this study as a subject with HI, an individual must meet all of the following criteria:

• Provision of signed and dated informed consent.
• Stated willingness to comply with all study procedures and availability for the duration of the study
• All genders, aged 18-80 years

Diagnosed with hearing instability, defined as documented hearing instability on serial audiometry with sensorineural hearing loss (SNHL) greater than 30 dB HL at one or more frequencies on at least one hearing test. Inclusion will require documentation of clinically significant change in hearing (either worsening or improvement) between at least 2 hearing tests or documentation of a sudden change in hearing. Clinically significant change in hearing will be defined by a change of10 dB at any three frequencies, 15 dB at any two frequencies, or at least 20 dB at one frequency. A sudden change in hearing will be defined as at least a 30 dB difference at 3 consecutive frequencies in the affected ear as compared to the contralateral ear.

• No air-bone gaps in excess of 10 dB for 500-4000 Hz indicative of conductive HL in at least 1 ear.
• For females of reproductive potential: Negative pregnancy test at start of study

Unaffected Adults

In order to be eligible to participate in this study as a healthy volunteer, an individual must meet all of the following criteria:

• Provision of signed and dated informed consent.
• Stated willingness to comply with all study procedures and availability for the duration of the study
• All genders, aged 18-80 years
• No air-bone gaps in excess of 10 dB for 500-4000Hz indicative of conductive HL in at least one ear.
• Normal middle ear function as indicated by normal 226 Hz tympanograms bilaterally, defined as middle ear pressure between plus minus 100 decaPascals, and peak compensated static compliance between 0.3-1.8 milliliters
• For females of reproductive potential: Negative pregnancy test at start of study

EXCLUSION CRITERIA

Affected and unaffected individuals who meet any of the following criteria will be excluded from participation in this study:

• Presence of non-MRI compatible devices (cardiac pacemaker, meta\<specific devices (e.g., cardiac pacemaker)
• Pregnancy or lactation
• Known allergic reactions to gadolinium
• Febrile illness within 2 weeks that could affect immune profiling*
• Evidence of active outer or middle ear disease or anomaly (e.g. otitis media, stenotic ear canal, otorrhea)
• History of chronic, as defined by fluid in the middle ear for more than 4 months, or recurrent otitis media, as defined by more than 4 episodes of acute otitis media in one year.
• Current PE tubes
• Bilateral profound (Pure tone average (PTA) > 90 dB HL) sensorineural hearing loss
• History or diagnosis of a central nervous system disorder, including but not limited to:

• Intracranial tumors
• Cerebrovascular disease
• Degenerative CNS disorder
• CNS trauma
• Encephalitis
• Meningitis
• Unable to discontinue medications that can interfere with vestibular test results for the 48 hours immediately preceding a vestibular study session. These include any and all anti-dizziness medications (such as Antivert), alcohol, caffeine, prescription pain medications (such as Percocet), prescription headache medications (such as Imitrex), sleeping pills (such as Ambien), anti-seizure medications (such as Topamax), and/or antihistamines (such as Benadryl).
• Current diagnosis from the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) of schizophrenia, bipolar disorder, or psychosis.
• Unstable intercurrent illness that in the judgment of the PI could prevent or confound collection of data.

Prospective study subjects who are cognitively impaired and lack consent capacity, will not be enrolled.

*Participants suspected of having COVID-19 will be moved to the designated COVID-19 unit and tested for SARS CoV-2 and Respiratory Pathogen Panel per guidance from NIH CC Clinical Practice Safety Guidelines. Possible COVID-19 infections identified by phone screen will not be eligible for study protocol until infection resolved.