Audiovestibular Function in Infratentorial Superficial Siderosis

Completed

Conditions: Neurological Disorder
Presbycusis
Age Related Hearing Loss
Siderosis
Rare Diseases

Registration Number: NCT04200664

Lead Sponsor: University College, London

Brief Summary: One in six people in the United Kingdom and over 400 million people worldwide have disabling hearing loss. This figure will double by 2050 as predicted by the World Health Organisation. There is an urgent need to improve our knowledge regarding hearing loss, its underlying mechanisms, optimal diagnostic modalities, reliable and accurate functional and imaging biomarkers.

A less-well studied condition associated with progressive hearing loss is infratentorial superficial siderosis (iSS). It results from iron deposition along the surfaces of brain structures which control hearing and balance. It is currently considered uncommon, but may well be under-recognised and therefore under-reported. Despite its severity, our current understanding of its impact on the hearing (auditory) and balance (vestibular) functions is limited, and this has an adverse impact on the treatment offered to these patients. Additionally, iSS patients have been reported to have cognitive impairment yet literature reports of cognitive assessment in iSS are few. The cognitive dysfunction may be specific to iSS or due to progressive hearing impairment or a combination of both, and further studies are required to establish this. Olfaction is also known to be affected in patients with iSS yet is rarely reported in the literature.

Due to the significant morbidity and progressive nature, there is a clear need to improve our understanding of the audiovestibular dysfunction resulting from iSS.

The aim of this study is to comprehensively assess audiovestibular function in iSS compared to age-related hearing loss and the controls/normative data and as a means to quantify deficits for monitoring disease progression and response to treatment, to assess the impact on the quality of life, to analyse clinically-obtained data (including imaging, cognitive and laboratory data), and correlate these with functional findings in iSS.

Detailed Description: This study focuses on a rare condition called infratentorial superficial siderosis (iSS)-a disease where iron gradually accumulates in the superficial layers of the brain and spinal cord. Over time, this buildup can damage the nerves responsible for hearing and balance amongst others, leading to symptoms like progressive hearing loss, dizziness, and problems with coordination. iSS has not been well studied in the past. The hearing and balance function in persons with iSS has been described as variable - meaning, there has not been a specific pattern of hearing loss or imbalance or dizziness that can be associated with iSS. The studies to date have been with small groups of patients but mainly case reports.

The aim of the AVISS study has been to address this gap in the knowledge. This study investigates how iSS affects hearing, balance, and even sense of smell by studying three groups of people:

1. People with iSS, who already have hearing and balance problems.

2. People with age-related hearing loss, to compare how hearing declines over time.

3. People with normal hearing, serving as a control group.

The study will take place over three years, using a range of tests to assess hearing and balance:

* Hearing tests like pure tone audiometry, speech-in-noise assessments, and auditory brainstem response.

* Balance tests such as vestibular evaluations, gait assessments, and head impulse testing.

* Olfactory (smell) tests, since iSS might also affect sensory perception. By collecting this data, the study aims to improve how iSS is diagnosed, identify better rehabilitation methods, and explore new treatment options for those affected.

The study is funded by NIHR UCLH Biomedical Research Centre and the Bernice Bibby Research Trust, ensuring experts have the resources needed to make meaningful discoveries. Ultimately, the goal is to help doctors recognize iSS earlier, support affected individuals more effectively and improve their overall quality of life.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 11

Inclusion Criteria

Siderosis group: adults (male and female) of 18+ years old with a known diagnosis of iSS (defined using standardised radiological criteria) confirmed by a consultant neurologist with expertise in this condition at University College London Hospitals National Health Service (NHS) Foundation Trust
Age-related hearing loss (ARHL) group: adults (male and female) of 18+ years old with ARHL
Control group: adults (male and female) of 18+ years old with no previous diagnosis of hearing loss or no known neurological disorder (including iSS) that affects hearing, with the aim to recruit such participants of 50 years of age and above; however, should difficulty with the recruitment of such participants arise, participants of 18 years of age and above will be invited to participate in the study.

Exclusion Criteria

All groups: individuals younger than 18 years old; individuals with a physical or mental impairment that prevents the potential participant from giving informed consent or undergoing the hearing and/or vestibular assessment;
Siderosis group: individuals with no prior diagnosis of iSS
Age-related hearing loss (ARHL) group: individuals with no previous diagnosis of ARHL or with a diagnosis of hearing loss of aetiology other than age-related; individuals with a history of exposure to high-intensity noise or ototoxic drugs or evidence of middle ear disease/dysfunction or family history of non age-related hearing loss;
Control group: individuals with a known history of hearing loss (of any cause) or with a known neurological disorder that affects their hearing; individuals with history of exposure to high-intensity noise or ototoxic drugs or evidence of middle ear disease or family history of non age-related hearing loss;

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Hearing Evaluation - Pure Tone Audiometry	Baseline visit	Clinical audiological (hearing) tests were performed to assess hearing function. The hearing tests included psychophysical, physiological and electrophysiological measures, (pure-tone audiometry, tympanometry, auditory brainstem responses and acoustic reflexes). The tests were perfomed in line with the procedure guidelines by the British Society of Audiology (www.thebsa.org.uk). The mean value of pure-tone audiometric thresholds for both ears measured in decibel hearing level (as described in the guidelines by the British Society of Audiology) was calculated and reported. Other parameters were reported as normal or abnormal (in at least one ear) or inconclusive.
Hearing Evaluation - Auditory Brainstem Responses/Acoustic Reflexes	Baseline visit	Clinical audiological (hearing) tests were performed to assess hearing function. The hearing tests included psychophysical, physiological and electrophysiological measures, (pure-tone audiometry, tympanometry, auditory brainstem responses and acoustic reflexes). The tests were perfomed in line with the procedure guidelines by the British Society of Audiology (www.thebsa.org.uk). The mean value of pure-tone audiometric thresholds for both ears measured in decibel hearing level (as described in the guidelines by the British Society of Audiology) was calculated and reported. Other parameters were reported as normal or abnormal (in at least one ear) or inconclusive.
Hearing Evaluation - Tympanogram	Baseline	Clinical audiological (hearing) tests were performed to assess hearing function. The hearing tests included psychophysical, physiological and electrophysiological measures, (pure-tone audiometry, tympanometry, auditory brainstem responses and acoustic reflexes). The tests were perfomed in line with the procedure guidelines by the British Society of Audiology (www.thebsa.org.uk). The mean value of pure-tone audiometric thresholds for both ears measured in decibel hearing level (as described in the guidelines by the British Society of Audiology) was calculated and reported. Other parameters were reported as normal or abnormal (in at least one ear) or inconclusive.
Hearing Evaluation - Otoacoustic Emissions	Baseline	Clinical audiological (hearing) tests were performed to assess hearing function. The hearing tests included psychophysical, physiological and electrophysiological measures, (pure-tone audiometry, tympanometry, auditory brainstem responses and acoustic reflexes). The tests were perfomed in line with the procedure guidelines by the British Society of Audiology (www.thebsa.org.uk). The mean value of pure-tone audiometric thresholds for both ears measured in decibel hearing level (as described in the guidelines by the British Society of Audiology) was calculated and reported. Other parameters were reported as normal or abnormal (in at least one ear) or inconclusive.
Vestibular/Balance Evaluation	Baseline visit	Clinical vestibular and balance tests were performed to assess vestibular/balance function.
Hearing Evaluation - Listening in Spatialised Sentences Noise Test	Baseline	Clinical audiological (hearing) tests were performed to assess hearing function. The hearing tests included psychophysical, physiological and electrophysiological measures, (pure-tone audiometry, tympanometry, auditory brainstem responses and acoustic reflexes). The tests were perfomed in line with the procedure guidelines by the British Society of Audiology (www.thebsa.org.uk). The mean value of pure-tone audiometric thresholds for both ears measured in decibel hearing level (as described in the guidelines by the British Society of Audiology) was calculated and reported. Other parameters were reported as normal or abnormal (in at least one ear) or inconclusive. Cameron S, Dillon H. The listening in spatialized noise-sentences test (LISN-S): comparison to the prototype LISN and results from children with either a suspected (central) auditory processing disorder or a confirmed language disorder. J Am Acad Audiol. 2008 May;19(5):377-91.

Secondary Outcome Measures

Name	Time	Method
Correlation Between Clinically Obtained Imaging (Siderosis Group Participants) and the Hearing and Balance Assessment Results	Baseline visit	Siderosis group participants underwent formal imaging procedures as part of their clinical care pathway. The imaging results were reviewed with the results obtained from hearing and vestibular/balance assessments. All participants had MRI Brain, as part of their clinical care pathway; susceptibility-weighted images were reviewed to identify the appearance of superficial siderosis, in keeping with the radiological diagnostic criteria (Reference: Wilson et al, 2017).
Correlation Between Clinically Obtained Results of Cognitive Function Assessment (Siderosis Group Participants) and the Hearing and Balance Assessments	Baseline visit	Siderosis group participants underwent a formal neuro-cognitive assessment as part of their clinical care pathway. The results of this clinical assessment were reviewed to determine if an association exists between the cognitive assessment results and the results obtained from hearing and vestibular/balance assessments performed during the study. A formal neuro-cognitive assessment was performed using the Wechsler Adult Intelligence Scale test. Cognitive impairment in a domain was defined as scoring at or below the fifth percentile on any one test in that domain.
Smell Identification Test	Baseline visit	University of Pennsylvania Smell Identification Test (UPSIT, British version) was performed (siderosis group participants) to assess their olfactory function. UPSIT is a forced-choice 40-item self-administered test. The scores are calculated using manufacturer's answer key as the sum of correct answers (maximum best = 40, minimum score 6; anosmia \<19(males, females); normosmia \>33 (males) and \>34 (females)), and compared to the age- and gender-matched norms. The scores are also grouped into categories (ranging from normosmia to anosmia), with higher scores indicating better olfactory function.

Trial Locations

Locations (2): UCL Ear Institute
🇬🇧
London, United Kingdom
University College London Hospitals NHS Foundation Trust
🇬🇧
London, United Kingdom
UCL Ear Institute
🇬🇧London, United Kingdom