AViSS: Audiovestibular Function in Infratentorial Superficial Siderosis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Siderosis (iSS) group participants with a known diagnosis of infratentorial superficial siderosis (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 |
Diagnostic Test: Hearing assessment
All study participants will undergo hearing tests, including hearing-specific questionnaires
Diagnostic Test: Vestibular/balance assessment
Siderosis group participants will undergo vestibular/balance tests, including gait assessment and balance-specific questionnaires
Other: Quality of life assessment
All study participants will be asked to complete a set of quality of life questionnaires
Diagnostic Test: Olfactory (smell) function testing
Siderosis group participants will undergo a formal smell identification testing by means of self-administered smell chart to identify the revealed scents
Genetic: DNA bio-banking
Siderosis group participants will be asked to provide a saliva sample for DNA bio-banking
|
| Age-related hearing loss (ARHL) group participants with age-related hearing loss (as identified from participant's clinical history and examination, with hearing thresholds confirmed on a pure-tone audiogram) |
Diagnostic Test: Hearing assessment
All study participants will undergo hearing tests, including hearing-specific questionnaires
Other: Quality of life assessment
All study participants will be asked to complete a set of quality of life questionnaires
|
| Control group participants with no known or previously reported hearing loss (as identified from participant's clinical history and examination, with hearing thresholds confirmed on a pure-tone audiogram) |
Diagnostic Test: Hearing assessment
All study participants will undergo hearing tests, including hearing-specific questionnaires
Other: Quality of life assessment
All study participants will be asked to complete a set of quality of life questionnaires
|
Outcome Measures
Primary Outcome Measures
- Hearing evaluation [Inclusion visit]
An array of audiological (hearing) tests will be performed to comprehensively assess hearing function in siderosis group participants and in age-related hearing loss and control groups. The hearing tests will include psychophysical, physiological and electrophysiological measures.
- Vestibular/balance evaluation [Inclusion visit]
An array of clinical vestibular and balance tests will be performed to comprehensively assess vestibular/balance function in siderosis group participants, including "scale for the assessment and rating of ataxia" and "functional gait assessment".
Secondary Outcome Measures
- Quality of life assessment [Inclusion visit and at 12 months]
Hearing-specific questionnaires and general quality-of-life questionnaires will be provided to all study participants to complete at their initial study visit and at 12-months (siderosis group participants will also be provided with balance-specific questionnaires).
- Correlation between clinically obtained imaging (siderosis group participants) and the hearing and balance assessment results [Inclusion visit]
Siderosis group participants will undergo formal imaging procedures as part of their clinical care pathway. The results of this clinical assessment will be correlated with the results obtained from hearing and vestibular/balance assessments performed during the study.
- Correlation between clinically obtained results of cerebrospinal fluid (siderosis group participants) and the hearing and balance assessments [Inclusion visit]
Siderosis group participants will undergo a formal assessment of cerebrospinal fluid as part of their clinical care pathway. The results of this clinical assessment will be correlated with the results obtained from hearing and vestibular/balance assessments performed during the study.
- Correlation between clinically obtained results of cognitive function assessment (siderosis group participants) and the hearing and balance assessments [Inclusion visit]
Siderosis group participants will undergo a formal neuro-cognitive assessment as part of their clinical care pathway. The results of this clinical assessment will be correlated with the results obtained from hearing and vestibular/balance assessments performed during the study.
- Smell Identification Test [Inclusion visit]
Smell Identification Test will be administered to siderosis group participants to assess olfactory function.
- DNA bio-banking [Inclusion visit]
Saliva samples for DNA bio-banking will be obtained from siderosis group participants.
Eligibility Criteria
Criteria
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
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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;
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Siderosis group: individuals with no prior diagnosis of iSS
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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;
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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;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCL Ear Institute | London | United Kingdom | ||
| 2 | University College London Hospitals NHS Foundation Trust | London | United Kingdom |
Sponsors and Collaborators
- University College, London
- NIHR UCLH BRC
- The Bernice Bibby Research Trust
Investigators
- Principal Investigator: Doris-Eva Bamiou, Professor, The Ear Institute, University College London; Department of Neuro-otology, University College London Hospitals NHS Foundation Trust, UK
- Principal Investigator: David J Werring, Professor, Department of Brain Repair and Rehabilitation, Stroke Research Centre, Institute of Neurology, University College London; Department of Neurology, University College London Hospitals NHS Foundation Trust, UK
Study Documents (Full-Text)
None provided.More Information
Publications
- Fearnley JM, Stevens JM, Rudge P. Superficial siderosis of the central nervous system. Brain. 1995 Aug;118 ( Pt 4):1051-66. Review.
- IWANOWSKI L, OLSZEWSKI J. The effects of subarachnoid injections of iron-containing substances on the central nervous system. J Neuropathol Exp Neurol. 1960 Jul;19:433-48.
- Koeppen AH, Dickson AC, Chu RC, Thach RE. The pathogenesis of superficial siderosis of the central nervous system. Ann Neurol. 1993 Nov;34(5):646-53.
- Kumar N. Superficial siderosis: associations and therapeutic implications. Arch Neurol. 2007 Apr;64(4):491-6. Review.
- Kwartler JA, De La Cruz A, Lo WW. Superficial siderosis of the central nervous system. Ann Otol Rhinol Laryngol. 1991 Mar;100(3):249-50.
- Offenbacher H, Fazekas F, Schmidt R, Kapeller P, Fazekas G. Superficial siderosis of the central nervous system: MRI findings and clinical significance. Neuroradiology. 1996 May;38 Suppl 1:S51-6. Review.
- Posti JP, Juvela S, Parkkola R, Roine S. Three cases of superficial siderosis of the central nervous system and review of the literature. Acta Neurochir (Wien). 2011 Oct;153(10):2067-73. doi: 10.1007/s00701-011-1116-0. Epub 2011 Aug 7. Review.
- Pribitkin EA, Rondinella L, Rosenberg Si, Yousem DM. Superficial siderosis of the central nervous system: an underdiagnosed cause of sensorineural hearing loss and ataxia. Am J Otol. 1994 May;15(3):415-8.
- Sydlowski SA, Cevette MJ, Shallop J. Superficial siderosis of the central nervous system: phenotype and implications for audiology and otology. Otol Neurotol. 2011 Aug;32(6):900-8. doi: 10.1097/MAO.0b013e31822558a9.
- Sydlowski SA, Levy M, Hanks WD, Clark MD, Ackley RS. Auditory profile in superficial siderosis of the central nervous system: a prospective study. Otol Neurotol. 2013 Jun;34(4):611-9. doi: 10.1097/MAO.0b013e3182908c5a.
- Takeda T, Kawashima Y, Hirai C, Makabe A, Ito T, Fujikawa T, Yamamoto K, Maruyama A, Tsutsumi T. Vestibular Dysfunction in Patients With Superficial Siderosis of the Central Nervous System. Otol Neurotol. 2018 Jul;39(6):e468-e474. doi: 10.1097/MAO.0000000000001844.
- van Harskamp NJ, Rudge P, Cipolotti L. Cognitive and social impairments in patients with superficial siderosis. Brain. 2005 May;128(Pt 5):1082-92. Epub 2005 Mar 23.
- Vibert D, Häusler R, Lövblad KO, Schroth G. Hearing loss and vertigo in superficial siderosis of the central nervous system. Am J Otolaryngol. 2004 Mar-Apr;25(2):142-9.
- Wilson D, Chatterjee F, Farmer SF, Rudge P, McCarron MO, Cowley P, Werring DJ. Infratentorial superficial siderosis: Classification, diagnostic criteria, and rational investigation pathway. Ann Neurol. 2017 Mar;81(3):333-343. doi: 10.1002/ana.24850. Epub 2017 Jan 28.
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